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Biomedical subjects

S Ono

Publications and source records attributed to S Ono.

At least 469 records · Page 26Linked to original sources

Regional myocardial perfusion and glucose metabolism in experimental left bundle branch block.

BACKGROUND: Several authors have reported cases in which 201Tl scintigraphy demonstrated perfusion abnormality in the septum of patients with left bundle branch block (LBBB) and normal coronary arteriogram. The mechanism of this abnormality, however, remains to be clarified. METHODS AND RESULTS: To determine whether LBBB itself induces abnormal myocardial perfusion and ischemia and to elucidate its mechanism, we used an in vivo animal model. LBBB was induced by right ventricular pacing in 17 open-chest dogs. We examined myocardial perfusion and glucose uptake using 201Tl and 18F-labeled 2-fluoro-2-deoxy-D-glucose. 201Tl activity in the septum was reduced to 74.7 +/- 14.5% of its maximal activity, and mean activity was 86.5 +/- 5.3% in the free wall (p less than 0.05). 18F activity in the septum was also reduced compared with that in the free wall (67.4 +/- 12.1% versus 88.0 +/- 5.2%, p less than 0.05). Regional myocardial blood flow was significantly reduced in the septum compared with the free wall, averaging 0.53 +/- 0.18 ml/min/g versus 0.84 +/- 0.14 ml/min/g, respectively (p less than 0.01). Systolic thickening in the septum was reduced from 1.36 +/- 0.20 to 0.98 +/- 0.04 (p less than 0.01) after the induction of LBBB, and the intramyocardial pressure in the septum in diastolic phase, in which the major flow of left anterior descending coronary artery (LAD) exists, increased from 26.6 +/- 10.5 to 57.8 +/- 22.2 mm Hg (p less than 0.02). Mean aortic pressure, LAD flow, and lactate extraction rate showed no significant change. CONCLUSIONS: LBBB itself may reduce myocardial perfusion and glucose uptake in the septum because of impaired systolic thickening and augmented intramyocardial pressure in the septum; however, this is not necessarily related to septal ischemia.

Animals↗

Amyotrophic lateral sclerosis: increased solubility of skin collagen.

We studied the solubility of skin collagen from six patients with amyotrophic lateral sclerosis (ALS) and six controls. The amount of collagen extracted with neutral salt solution was significantly greater in patients with ALS than in controls. In addition, there was a statistically significant increase in the proportion of collagen extracted from ALS patients with increased duration of illness. The collagen solubilized by pepsin and cyanogen bromide treatments was significantly higher in ALS patients than in controls, and its proportion was positively and significantly associated with duration of illness in ALS patients. These results indicate that the metabolism of skin collagen may be affected in the disease process of ALS, causing an increase in immature soluble collagen in the tissue, which is the opposite to that which occurs in the normal aging process.

Amyotrophic Lateral Sclerosis↗

Effect of diltiazem on stunned myocardium evaluated with 99mTc-pyrophosphate imaging in canine heart.

The effect of diltiazem on stunned myocardium was evaluated by measuring the myocardial uptake of 99mTc-PYP (pyrophosphate) in open chest experiments with dogs. Myocardial stunning was induced by a 30 min ischemic occlusion of the anterior descending coronary artery. Regional wall motion was monitored by echocardiography of the epicardium for 2 h during reperfusion. After a 30 min occlusion of the coronary artery, it was reperfused and 99mTc-PYP was injected, followed by 201Tl 2 h later. The ischemic area was defined by Evans blue dye, and the infarct area by TTC staining. No dogs showed infarcts or 201Tl defects in this study group. Five dogs of the control-1 group (C1, ischemic area = 19.1 +/- 3.2%) showed decreased regional wall motion during occlusion (15.5 +/- 3.5% of control), and a slow recovery from depressed motion after 2 h of reperfusion (20.3 +/- 9.3%) with uptake ratio (compared to the non-ischemic area uptake) of 99mTc-PYP (4.96 +/- 2.28). In contrast, both groups with diltiazem infusion (20 micrograms/kg/min), started either 30 min before ischemia (D1 = 5 dogs) or just after reperfusion (D2 = 5 dogs), showed significantly better recovery after 2 h of reperfusion (D1:115.4 +/- 36.0%, D2:109.2 +/- 44.2%) than C1 (p less than 0.05), D1 and D2 groups also showed suppressed 99mTc-PYP uptake ratio (D1:1.06 +/- 0.33, D2:2.34 +/- 2.05, p less than 0.05 vs C1) in spite of comparable ischemic area. Four dogs with small ischemic area (C2:5.3 +/- 5.0%) did not show increased 99mTc-PYP uptake (1.15 +/- 0.35), and regional wall motion after 2 h of reperfusion was 96.1 +/- 24.1% of the control value (p less than 0.05 vs C1). Thus, diltiazem was effective in enhancing the suppression of 99mTc-PYP uptake in the stunned myocardium, and similar results were obtained for small ischemic areas. The protective effect of diltiazem appears to be strongly related to the mechanism of 99mTc-PYP uptake.

Animals↗

Advances in transesophageal echocardiography for the evaluation of atherosclerotic lesions in thoracic aorta--the effects of hypertension, hypercholesterolemia, and aging on atherosclerotic lesions.

We assessed atherosclerotic lesions in the thoracic aorta in 166 consecutive patients (aged 56 +/- 13 years) by transesophageal echocardiography, and investigated the influences of hypertension, hypercholesterolemia and age on the prevalence of such lesions. Satisfactory images were obtained of all the thoracic aorta, except for a small part of the ascending aorta, by use of a biplane transesophageal probe. We defined atherosclerotic lesions as increased echogenicity of the intima (intimal thickening), raised plaque, calcification, ulceration, or aneurysms. Lesions were observed in 97 patients (58%). The incidence of lesions in patients with hypertension (81%) or hypercholesterolemia (80%) was significantly greater than in those without both conditions (37%, p less than 0.005). The incidence of lesions was significantly increased among patients over 60 years old compared with that in patients under 60 (76% vs 42%, p less than 0.005). Patients without either hypertension or hypercholesterolemia showed a marked increase in the incidence of lesions with age (16% at less than 60 yrs vs. 67% at greater than 60 yrs), and no significant influence of these conditions on the incidence of lesions was found in patients over 60. We conclude that hypertension and hypercholesterolemia might be important risk factors for the development of atherosclerotic lesions in the thoracic aorta in relatively younger patients. Age appears to become a more important determinant of such lesions in Japanese patients over 60 years old irrespective of blood pressure and serum cholesterol levels.

Adult↗

Positron emission tomography--usefulness in assessing myocardial viability.

Positron emission tomography (PET) using N-13 ammonia and F-18 fluorodeoxyglucose (FDG) has been used to evaluate myocardial viability in comparison with thallium-201 single photon emission computed tomography (SPECT), and left ventricular wall motion in comparison with contrast ventriculography. Forty patients with anterior myocardial infarction underwent stress and delayed resting perfusion imaging using Tl-201 SPECT and ammonia PET, a glucose metabolism study using FDG PET, and wall motion assessment with left ventriculography. Out of a total of 600 segments of left ventricular imaging, SPECT demonstrated 197 fixed perfusion defects, 99 with redistribution on delayed imaging and 304 normal segments. Of 197 segments with fixed defects, 24 (12%) were normal and 71 (36%) ischemic according to PET criteria. Nineteen of 28 with infarction and all of 12 with non-Q wave infarction showed a viable myocardium. Left ventricular wall motion was significantly better in patients with normal PET findings compared with those with ischemia or scar on PET. Post-PTCA PET revealed improved ammonia PET in 6 of 11 patients but reduced FDG uptake was noted only in 3. These data suggests that Tl-201 SPECT significantly underestimates myocardial viability and that PET imaging is a promising tool for assessing the presence of salvaged myocardium.

Angioplasty, Balloon, Coronary↗

[Etoposide and cisplatin combination chemotherapy in a patient with small cell lung carcinoma under artificial hemodialysis].

A 70-year-old man with small cell carcinoma of the lung who was under artificial hemodialysis, was treated by combined administration of etoposide and cisplatin. Fifty mg. of etoposide in combination with 35 mg. of cisplatin were infused before dialysis. Before one hour and during dialysis, plasma etoposide and platinum levels decreased rapidly. No severe side effect was observed after the administration of etoposide and cisplatin. In conclusion, it was considered that cisplatin and etoposide could be given to the patient with malignant tumor under artificial hemodialysis.

Aged↗

[Surgery for the patients whose total pulmonary vascular resistance was over 700 dyne during unilateral pulmonary artery occlusion test].

To determine the indication for surgery from the point of pulmonary function, we have performed the unilateral pulmonary artery occlusion test in lung cancer patients. In these patients, we gave a surgery in 13 cases whose total pulmonary vascular resistance were over 700 dyne.sec.cm-5/M2 per body surface area. The pulmonary hemodynamics before and during pulmonary artery occlusion were 549 +/- 82 and 798 +/- 78 dyne.sec.cm-5/M2 in total vascular resistance, 18.7 +/- 3.8 and 27.2 +/- 4.3 cmHg in mean pulmonary arterial pressure and 2.69 +/- 0.36 and 2.73 +/- 4.3 L/min/M2 in cardiac index respectively. In 7 cases out of 13, we performed selective pulmonary artery occlusion test. In pulmonary function test, 10 cases had a chronic obstructive diseases, 2 cases had a disturbance of diffusion and one case has a contractive disease. We gave a lobectomy in 12 cases and completion pneumonectomy in one case. Two of lobectomy cases died in the early phase: 42 and 72 days after surgery due to pulmonary complications. One of these cases needed an additional completion pneumonectomy because of bronchial fistel. Surgical complications were seen in 12 cases. These 13 cases used to be recognized that they have no indication of surgery because of low pulmonary function, however it revealed that we can give a lobectomy through a high intensive care after surgery.

Adenocarcinoma↗

Analysis of a unique molecule responsible for regeneration and stabilization of differentiated state of tissue cells.

In Wolffian regeneration in the newt, a functional lens can be regenerated through cellular transdifferentiation of the pigmented epithelium of the mid-dorsal marginal iris. A novel monoclonal antibody, 2NI-36 mAb, generated in our laboratory has been utilized as a highly useful probe to study newt lens regeneration. The antigen molecule against this 2NI-36 mAb (2NI-36) became temporarily undetectable only at the site of lens regeneration. Moreover, the ventral iris pieces expressed the ability to differentiate a lens when pretreated with this monoclonal antibody and implanted in lentectomized eyes (Eguchi, Cell Differ. Dev. 25, Suppl., 1988). We have investigated the distribution of 2NI-36 in newt tissues. 2NI-36 was not specific to iris pigmented epithelium and distributed in many different kinds of mesodermal tissues, including dermis, blood vessel, mesonephros and so forth. 2NI-36 was also detected in either cell surface or intercellular spaces of cultured pigmented epithelial cells when they organized an epithelial cell sheet. Western blot analysis showed that 2NI-36 had the molecular weight of 50-200kD and was completely digested by trypsin, suggesting that 2NI-36 was a glycoprotein with many carbohydrate chains. It was also revealed by Western blot analysis that all the tissues in which 2NI-36 could be detected expressed this molecule similar to that in the iris epithelium. We expect that 2NI-36 is a glycoprotein expressed by various newt tissues and is functional to stabilize the differentiated state of each tissue cell in the same way as observed in the iris pigmented epithelial cells.

Animals↗

[A fundamental study of 99mTc-ethyl cysteinate dimer (99mTc-ECD)].

In vitro fundamental studies of 99mTc-ethyl cysteinate dimer (99mTc-ECD), a newly developed radiopharmaceutical for cerebral perfusion scintigraphy, were performed, and were compared with those of 99mTc-HM-PAO, which has been widely applied to clinical use. 99mTc-HM-PAO should not only be injected soon after reconstitution, but also be avoided mixture with saline or drugs such as Diamox, because of its radiochemical purity decreases with the passage of time and the addition of saline and Diamox. On the other hand, the radiochemical purity of 99mTc-ECD reached a constant level of 94-96% at 30 to 180 min after reconstitution, and it remained stable against the addition of saline and Diamox. Therefore, it was suggested that 99mTc-ECD could be injected from an already saline-infused venous-line or mixed with Diamox. However, early injection after reconstitution should be avoided, because 99mTc-ECD did not become stable enough to maintain sufficient radiochemical purity until 30 min after reconstitution. The present studies are suggested that the red blood cell component is largely related to the metabolism of 99mTc-ECD in blood. Furthermore, from study of the metabolic rate using rabbit blood, it was suggested that a species difference existed in esterase activity in blood.

Animals↗

[Usefulness of 99mTc-ECD SPECT in diseases of the central nerve system: special reference to a comparison with 123I-IMP and 99mTc-HM-PAO SPECT].

The usefulness of a new cerebral perfusion imaging radiopharmaceutical, 99mTc-ethyl cysteinate dimer (ECD), was clinically evaluated. The subjects of this study were 14 patients with neurological disorders including 10 patients with cerebral infarction and 4 patients with other diseases. A total of 15 examinations was performed. 99mTc-HM-PAO or 123I-IMP SPECTs were performed simultaneously, and the findings from those examinations were compared with 99mTc-ECD. As to the count ratio of lesions to normal area (L/N), the L/N ratio in severe ischemic patients was lower in 99mTc-ECD than in 99mTc-HM-PAO or 123I-IMP. In mild ischemic patients, on the other hand, the L/N ratio was the lowest in 123I-IMP. When the relationship between rCBFs obtained from 123I-IMP and the values of L/N in 99mTc-ECD or 99mTc-HM-PAO was compared, the values of L/N in 99mTc-ECD or 99mTc-HM-PAO were found to have decreased linearity with increasing rCBF. In a patient showing luxury perfusion, the accumulation pattern of 99mTc-ECD was different from that of the other two radiopharmaceuticals, and focal defect was revealed in 99mTc-ECD SPECT. On the dynamic SPECT of 99mTc-ECD in a patient with meningioma, the tumor showed a change from high to low perfusion with the passage of time. This finding indicated that care should be taken in the evaluation of accumulation of 99mTc-ECD. Therefore, 99mTc-ECD was found to be useful as a cerebral perfusion agent. In addition, as accumulation of 99mTc-ECD might somehow reflect metabolism in some cases, further careful investigation of many cases should be carried out.

Adult↗

[Extrapleural approach for patent ductus arteriosus and coarctation of the aorta].

During the period of 1989 to 1990, 6 consecutive children with patent ductus arteriosus or coarctation of the aorta underwent operative therapy. Ligation or division of patent ductus arteriosus or subclavian flap angioplasty for coarctation of the aorta were performed by extrapleural approach with axillary or posterolateral incision. Patients' ages ranged from 9 days to 8 years. Weights ranged from 3 to 30 kg. It was very easy to have better operative field and beneficial to protect the lung against mechanical injury. Extrapleural approach was not so easy in an 8-year-old patient with firm connective tissue. Therefore, this procedure is considered to be suitable for younger children.

Aortic Coarctation↗

Interaction with phospholipid bilayers, ion channel formation, and antimicrobial activity of basic amphipathic alpha-helical model peptides of various chain lengths.

Basic amphipathic alpha-helical peptides Ac-(Leu-Ala-Arg-Leu)3 or 4-NHCH3 (4(3) or 4(4)) and H-(Leu-Ala-Arg-Leu)3-(Leu-Arg-Ala-Leu)2 or 3-OH (4(5) or 4(6)) were synthesized and studied in terms of their interactions with phospholipid membranes, biological activity, and ion channel-forming ability. CD study of the peptides showed that they form alpha-helical structures in the presence of phospholipid liposomes and thus they have amphipathic distribution of the side chains along the axis of the helix. A leakage study of carboxyfluorescein encapsulated in phospholipid vesicles indicated that the peptides possess a highly potent ability to perturb the membrane structure. Membrane current measurements using the planar lipid bilayer technique revealed that the peptide 4(6), which was long enough to span the lipid bilayer in the alpha-helical structure, formed cation-selective ion channels at a concentration of 0.5 microM in a planar diphytanoylphosphatidylcholine bilayer. In contrast, other shorter peptides failed to form discrete and stable channels though they occasionally induced an increase in the membrane current with erratic conductance levels. The probability of detecting a conductance increase was in the order of 4(6) greater than 4(5) greater than 4(4) greater than 4(3), which corresponds to the order of the peptide chain lengths. Furthermore, 4(6) but not 4(5) showed an antimicrobial activity against both Gram-positive and -negative bacteria. The structure of ion channels formed by 4(6) and the relationship between the peptide chain length and biological activity of the synthetic peptides are discussed.

Amino Acid Sequence↗

Conformational studies of amphipathic alpha-helical peptides containing an amino acid with a long alkyl chain and their anchoring to lipid bilayer liposomes.

In order to investigate the conformation and orientation of lipid-bound peptides and proteins in the lipid bilayer, basic amphipathic alpha-helical peptides with a long alkyl chain, palmitoyl-(Leu-Ala-Arg-Leu)3-NHCH3 (P-4(3)) and Ac-Leu-Ala-Arg-Leu-Trp-Amy-Arg-Leu-Leu-Ala-Arg-Leu-NHCH3 (Amy-4(3), Amy; alpha-aminomyristic acid) were designed and synthesized. The conformational features and spectroscopic behavior in a buffer solution and in neutral and acidic liposomes were studied by CD, dye-leakage, and fluorescence measurements. The CD data indicated that P-4(3) took an alpha-helical structure in aqueous solution and in neutral and acidic liposomes. On the other hand, Amy-4(3) took a beta-structure in aqueous solution and an alpha-helical structure in neutral and acidic liposomes. The conformational change of Amy-4(3) was confirmed by fluorescence study on lipid titration of the peptide. The dye-leakage experiment showed that both peptides interacted with acidic liposomes to perturb them, but less effectively than Ac-(Leu-Ala-Arg-Leu)3-NHCH3 (4(3)) which has no long alkyl group. Based on these results, a discussion is made concerning the conformation and orientation of peptides in aqueous solution and in the lipid bilayer.

Amino Acid Sequence↗

Photodynamic therapy using pheophorbide-a and Q-switched Nd:YAG laser on implanted human hepatocellular carcinoma.

To evaluate whether administration of pheophorbide-a, a new photosensitizer, followed by use of Q-switched Nd:YAG laser produces a photodynamic reaction, we administered pheophorbide-a to female nude mice (BALB/c-nu) that had been implanted with human hepatocellular carcinoma. Intra-tumoral concentrations of pheophorbide-a were measured by high-performance liquid chromatography. 3 hours after peroral administration of 1 mg/kg body weight, the intra-tumoral concentration was too low to reveal photodynamic effects. Peroral administration of 250 mg/kg body weight, intra-peritoneal administration of 5 mg/kg body weight, and intra-tumoral injection of 200 micrograms yielded 0.24 micrograms/g, 0.83 micrograms/g and 3.68-108 micrograms/g tumor concentrations, respectively. All tumors were irradiated interstitially using a Q-switched Nd:YAG laser at 1064 nm. Only tumors that had been intra-tumorally injected had areas of necrosis larger than those in control tumors. The results suggest that the injection of pheophorbide-a followed by interstitial irradiation using a Q-switched Nd:YAG laser does not induce sufficient photodynamic reaction if the intra-tumoral pheophorbide-a concentration is less than 0.83 micrograms/g tumor tissue, and that photodynamic therapy may be useful if the pheophorbide-a tumor concentration is within the range of 0.83-108 micrograms/g.

Animals↗

Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by alpha-adrenergic receptor antagonists.

Effects of clonidine and tizanidine, which have antinociceptive and alpha 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2-3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the cord tissue to 10 microM clonidine and tizanidine significantly reduced the release of substance P. The inhibitory effects of clonidine and tizanidine were attenuated by pre-exposure of the tissue to 10 microM piperoxane, which has alpha 2-antagonistic activity and the inhibitory effect of clonidine was attenuated by 10 microM yohimbine. Moreover, the inhibitory effects of clonidine and tizanidine were also blocked by a small dose of prazosin, an antagonist for alpha 1- and alpha 2B-receptors. None of the antagonists had any effect on release of substance P, when given alone. These results suggest that alpha 2B-adrenoceptors are involved in the inhibitory effects of clonidine and tizanidine on the release of substance P.

Adrenergic alpha-Antagonists↗