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Biomedical subjects

Y Isaka

Publications and source records attributed to Y Isaka.

105 records · Page 6Linked to original sources

[Cerebral perfusion imaging with N-isopropyl-(123I) P-iodoamphetamine (123I-IMP): its planar imaging and semiquantitative analysis in cases with internal carotid occlusion].

Occlusion of internal carotid artery (ICA) is one of the most common cause of stroke, and the single common arterial lesion considered for extraintracranial bypass. The symptoms of ICA occlusion are not uniform; some shows transient ischemic attacks (TIAs), others completed stroke at the onset. So, measurement of cerebral blood flow might be needed to evaluate the prognosis, or to select surgical candidate in ICA occlusion. Several methods, such as Xe-133 intracarotid method, Xe-133 inhalation method etc, have been applied for the assessment of cerebral blood flow in cases with ICA occlusion. No previous report was found by the newly developed 123I-IMP in this connection. The purpose of the present study is first to demonstrate the feasibility of 123I-IMP planar brain scintigraphy and its semiquantitative analysis in 17 cases with ICA occlusion. After intravenous injection of 3 mCi of 123I-IMP, brain scintigrams were obtained from anterior, Towne, vertex, posterior, right lateral and left lateral views, and were recorded on magnetic tape and Poraloid films. Semiquantitative analysis was performed as a percent index of asymmetry (PIA) from the difference of each hemispheric count in the scintigrams by use of on-lined minicomputer system. Clinical manifestations of these 17 cases were, completed stroke in 10, TIAs in 4, and no neurological symptom in 3. 123I-IMP brain scintigrams demonstrated low flow lesion in 10 out of 10 completed stroke, in 2 out of 4 TIAs and normal perfusion in all cases with no neurological symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Platelet accumulation in carotid atherosclerotic lesions: semiquantitative analysis with indium-111 platelets and technetium-99m human serum albumin.

To evaluate platelet accumulation in carotid atherosclerotic lesions semiquantitatively, a dual-tracer technique was applied, using In-111 platelets and Tc-99m human serum albumin. With this approach, we investigated the ratio of radioactivity in In-111 platelets deposited on the vascular wall to those circulating in the blood pool, platelet accumulation index ( PAI ). This study included 12 normal subjects and 25 patients with ischemic cerebrovascular disease (CVD). Angiographic abnormalities were observed at 34 of 50 carotid bifurcations in the CVD patients. The mean PAI value was significantly higher at the carotid bifurcations with angiographic abnormality than at the normal ones (p less than 0.001). Furthermore, elevations of mean PAI were prominent at the lesions with severe stenosis or ulceration. The degree of platelet accumulation was well demonstrated by this technique, which can also yield information on thrombogenicity and efficiency of antiplatelet therapy in carotid atherosclerotic disease.

Adult↗

Platelet hyperaggregability in ischemic cerebrovascular disease and effects of aspirin.

Platelet aggregation was studied in 24 patients in the chronic stage of ischemic cerebrovascular disease (CVD), with cerebral affluent and effluent blood, i.e., carotid arterial and internal jugular venous blood, and also with peripheral venous blood. Aggregation tests were performed at various final concentrations of sodium arachidonate (A.A.) and ADP. In 17 patients, not taking aspirin, platelet aggregability in jugular venous blood was significantly accentuated compared with that in arterial and peripheral venous blood. This tendency was more marked in the patients with cerebral artery stenosis and/or occlusion than in those with normal cerebral angiogram. In 7 patients taking 500 mg or more oral aspirin, aggregation differences across the brain were not observed and A.A. aggregation and the second phase of ADP aggregation were completely suppressed. These results suggest that a prophylactic administration of aspirin may be beneficial for patients in chronic stage of CVD.

Arteries↗

Cerebral perfusion imaging with albumin microspheres tagged with Tc-99m and In-111 in cases with internal carotid occlusion.

Cerebral perfusion imaging with dual-tracer (Tc-99m and In-111) human albumin microspheres (HAM scintigraphy) was performed in 15 cases with unilateral occlusion of the internal carotid artery, for the diagnosis and evaluation of collateral circulation patterns. After injection of Tc-99m microspheres into one common carotid artery and In-111 HAMs into the other, two perfusion images, one for each carotid artery, were clearly differentiated by appropriate pulse-height discrimination. With this method, diagnosis of internal carotid artery occlusion was definitely made in eight patients, suspected in six, and missed in one. The collateral perfusion areas from the contralateral ICA and ipsilateral external carotid artery were well demonstrated by this method, and the scintigraphic results agreed well with the angiographic findings in all cases. Dual-tracer HAM scintigraphy is capable of adding information about collaterals at the capillary level to the anatomic information obtained by angiography.

Aged↗

Structural requirement of sterol side chain for the silkworm growth and development.

Several cholesterol analogs with modifications in the side chain were added to the artificial diet of the silkworm, and their effects on insect growth and development were determined. It was found that slight deviations of the cholesterol's side chain induced pronounced growth-retarding effects, suggesting an important functional role of the isooctane side chain of cholesterol.

Animals↗

Effects of hematocrit variations on cerebral blood flow and oxygen transport in ischemic cerebrovascular disease.

The contribution of hematocrit (Ht) changes on cerebral blood flow (CBF) and brain oxygenation in ischemic cerebrovascular disease is still controversial. In the present study, effects of Ht variations of CBF and oxygen delivery were investigated in patients with ischemic cerebrovascular disease. CBF was measured by the Xe-133 intracarotid injection method in 27 patients, whose diagnoses included completed stroke, reversible ischemic neurological deficit, and transient ischemic attack. Ht values in the patients ranged from 31 to 53%. There was a significant inverse correlation between CBF and Ht in these Ht ranges. Oxygen delivery, i.e., the product of arterial oxygen content and CBF, increased with Ht elevation and reached the maximum level in the Ht range of 40-45% and then declined. The CBF-Ht and oxygen transport-Ht relations observed in our study were similar to those in the glass-tube model studies by other workers rather than to those in intact animal experiments. From these results, it is conceivable that in ischemic cerebrovascular disease, the vasomotor adjustment was impaired in such a manner that the relations among Ht, CBF, and oxygen delivery were different from those in healthy subjects. Further, an "optimal hematocrit" for brain oxygenation was also discussed.

Adolescent↗

Imaging analysis of platelet deposition on the extracardiac valved conduit in humans.

In 14 patients (aged 2-29 yr) with Hancock (n = 11) or Carpentier-Edwards extracardiac valved conduits (n = 3), platelet deposition (PD) was investigated using indium 111 (111In) platelet imaging. Repeated studies were performed in five patients. By visual analysis, 71% (5/7) of the imagings (7 images/5 patients) showed PD at early study 1-3 months after surgery, 9% (1/11) at intermediate study at 6-46 months (mean 21 mon) (11 images/10 patients) and 0% at late study at 81-132 months (3 images/3 patients). Quantitative analysis was made using relative ratio of radioactivity at the graft area to the area of the brachiocephalic artery (platelet accumulation index or PAI). The PAI was 1.85 +/- 0.47 (mean +/- SD) at early study, 1.51 +/- 0.23 at intermediate, and 1.36 +/- 0.37 at late study (NS). There was no significant difference in the late pressure gradients across the conduit (16-68 mon postoperatively) between the two groups with (n = 3) and without (n = 5) PD at the early stage (1-18 mon postoperatively, n = 8). The result may indicate that PD to the valved conduit in the right ventricular (RV) outflow tract occurs early postoperatively (mostly within 3 mon). The relationship of the PD detected by this method to late obstruction was not clarified in this study.

Adolescent↗

The HVJ liposome method.

Recent advancement of gene technology allows us a practical approach to gene therapy. Among various in vivo gene transfer techniques available, the HVJ liposome method is an efficient procedure which could target the glomerular cells. Using this method, HVJ-mediated cell fusion activity enables us to introduce genetic materials directly into the cytosol without degradation. In addition, cointroduction of non-histone nuclear protein, high-mobility group (HMG-1), efficiently facilitates migration of foreign DNA to the nucleus. Although there still exist some limitations, the HVJ liposome method may be applicable to the treatment of glomerular diseases as well as to analysis of the molecular aspects of renal pathophysiology.

Animals↗

Glowing podocytes in living mouse: transgenic mouse carrying a podocyte-specific promoter.

Green fluorescence protein (GFP) has been utilized as a marker of gene expression due to the great advantage in its simple and quick detectability. We generated transgenic mice carrying a GFP cDNA under the control of a beta-actin/beta-globin promoter (CX promoter) and cytomegalovirus enhancer. The green luminescence derived from GFP was apparent in skeletal muscle, pancreas, heart and kidney, but not in other tissues. The GFP expression in the kidney was localized in podocytes. Moreover, in situ hybridization of GFP showed that the transcriptional level was highly active in the podocytes. These results suggested that the glowing green fluorescence would be a useful in vivo marker of podocyte in these transgenic lines in the physiological and pathophysiological state, and that the CX promoter could allow a podocyte-specific expression of a molecule of interest in kidney.

Animals↗

The effect of a thromboxane synthetase inhibitor, OKY-046, on urinary excretion of immunoreactive thromboxane B2 and 6-keto-prostaglandin F1 alpha in patients with ischemic cerebrovascular disease.

Thromboxane synthetase activity is selectively inhibited by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046). A single dose of 100 mg OKY-046 was orally administered to patients with ischemic cerebrovascular disease and healthy volunteers. Platelet aggregation and thromboxane B2 (TXB2) generation of intact and homogenised platelets induced by 1.0 mM sodium arachidonate were measured before and at 1, 4, 6 and 8 h after dosing. OKY-046 inhibited arachidonate-induced aggregation in platelet rich plasma from some, but not all, individuals, whereas platelet TXB2 generation was almost completely inhibited by a single dose of 100 mg OKY-046, in all of the patients and healthy volunteers. Endogenous TXA2 and prostacyclin (PGI2) biosynthesis were assessed by measurement of urinary immunoreactive TXB2 (i-TXB2) and 6-keto-PGF1 alpha (i-6-keto-PGF1 alpha) before and at 0-3, 3-6, 6-9 h after dosing. OKY-046 increased the urinary i-6-keto-PGF1 alpha coincidently with a decrease of urinary i-TXB2, both in patients and healthy volunteers. These effects of a selective thromboxane synthetase inhibitor will improve a disturbed balance between TXA2 and PGI2, associated with the development of ischemic cerebrovascular disease.

6-Ketoprostaglandin F1 alpha↗

Effect of aspirin and ticlopidine on platelet deposition in carotid atherosclerosis: assessment by indium-111 platelet scintigraphy.

The antiplatelet effects of aspirin and ticlopidine were studied by a dual-tracer method, using indium-111 labeled platelets and technetium-99m human serum albumin, in a group of 12 patients with suspected ischemic cerebrovascular disease. The magnitude of platelet accumulation at the carotid bifurcation was expressed as the ratio of radioactivity of indium-111 platelets deposited on the vascular wall to those circulating in the blood-pool (PAI, platelet accumulation index), 48 hr after injection of labeled platelets. PAI values were measured before (baseline studies) and after the antithrombotic therapies (aspirin studies: 325 mg bid for 22.3 +/- 1.3 days, ticlopidine studies: 100 mg tid for 21.8 +/- 2.1 days). At the baseline, the mean PAI value at 24 carotid bifurcations in the patient group was 15.7 +/- 15.3% (mean +/- S.D.) compared to -4.3 +/- 9.1 at 24 carotid bifurcations in 12 normal subjects (p less than 0.01). We defined the upper limit for a normal PAI (%) value to be +13.9, namely the mean PAI plus 2 SD for the carotid bifurcation in normal subjects and used this value for semiquantitative analysis. At the baseline, significant elevation of PAI (more than 13.9%; positive scintigram) was observed at 12 of 24 vessels, while 12 other regions were negative (less than 13.9%). In the lesions with positive scintigraphic results at the baseline, the mean PAI (%) value from the baseline, aspirin and ticlopidine studies was 29.5 +/- 7.0, 11.2 +/- 8.5 (p less than 0.01 versus baseline) and 21.4 +/- 21.3 (not significant from baseline), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gene transfer and kidney disease.

There is little doubt that molecular biological intervention therapy has come of age and its potential is arousing tremendous excitement. A gene transfer technique, the HVJ-liposome method, is now applicable as a tool for the dissection of molecular aspects in the pathophysiology of renal diseases, and for gene therapy in experimental glomerulonephritis. Overexpressed transforming growth factor (TGF)-beta in the normal rat glomeruli, by gene transfer of TGF-beta cDNA, leads to glomerulosclerosis. However, inhibition of the TGF-beta action by antisense oligonucleotides can suppress the development of the experimental glomerulonephritis. We investigated whether in vivo gene transfer of chimeric proteins, composed of the extracellular domain of TGF-beta type II receptor fused with IgC-Fc, suppresses experimental glomerulonephritis. The expression of TGF-beta in glomeruli was suppressed and so was the extracellular matrix expansion. Taken together with clinical observation of up-regulation of TGF-beta in various glomerulopathies, the dys-regulation of the TGF-beta is important in the development of glomerulosclerosis, and manipulation of this overexpression may prove a novel therapeutic approach for slowing the progression of the disease.

Gene Transfer Techniques↗