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Biomedical subjects

Y Isaka

Publications and source records attributed to Y Isaka.

At least 91 records · Page 5Linked to original sources
PubMed1991

Multiple cerebral infarcts caused by emboli from carotid atheroma--a case confirmed by indium-111 platelet scintigraphy.

A 47-year-old male presented with frequent transient ischemic attacks (TIAs) of weakness of the left upper extremity. Computed tomography demonstrated multiple infarcts in the right cerebral hemisphere. Cerebral angiography showed marked atheromatous changes at the siphon of the right internal carotid artery, characterized by wall irregularities and heterogeneous filling. Indium-111-labeled platelet scintigraphy demonstrated abnormal tracer accumulation at the right carotid siphon. Following right carotid artery ligation, this abnormal platelet deposition was resolved and no further TIA was experienced. This suggests that the release of microthrombi from thrombogenic carotid atheroma contributes to embolic stroke.

Arteriosclerosis↗
PubMed1991

[Cerebral blood flow velocity measurements by transcranial Doppler during postural changes and walking in idiopathic orthostatic hypotension].

Transcranial Doppler (TCD) was utilized to estimate the cerebral blood flow velocity during postural changes or walking in two patients with idiopathic orthostatic hypotension (IOH). The probe of TCD was attached tightly to the temporal skull with a headband to measure the flow velocity of middle cerebral artery (MCA). The patients' postures were altered passively by a tilting table or actively by standing up or walking with their own feet. The TCD study clearly demonstrated a complete loss of autoregulation in Case 2 and an incomplete impairment of autoregulation in Case 1. In both patients, the blood pressure dropped markedly at a standing position, and MCA flow velocity decreased accordingly resulting in manifestation of dizziness. In Case 1, the blood pressure was elevated during walking, and MCA flow velocity increased leading to the improvement of ischemic symptoms. In Case 2, the TCD study was repeated after administration of fluorohydrocortisone, a mineralocorticoid agent, which ameliorated clinical symptoms. The results, however, indicated no improvement of autoregulatory response. The amelioration of symptoms was attributable to the elevation of blood pressure levels. Our study indicates the capability of TCD to estimate cerebral blood flow alteration during postural changes or walking. The TCD appears to be useful for evaluating the autoregulatory response and effectiveness of therapy in patients with orthostatism, like IOH.

Aged↗
PubMed1991

[Effect of white matter lesions on cerebral blood flow in asymptomatic individuals: assessment by MRI and 133Xe-CBF method].

In 32 patients with asymptomatic white matter lesions (WMLs), we evaluated the age-related changes in the number of white matter lesions, cerebral blood flow (CBF), cerebrovascular resistance (CVR) and mean arterial blood pressure (MABP). CBF was measured with the intravenous 133Xe injection method. The number of WMLs in whole brain was measured by the magnetic resonance imaging. CBF decreased with advancing age (r = 0.529; p less than 0.01), while the number of WMLs (r = 0.39; p less than 0.05), CVR (r = 0.464; p less than 0.01) and MABP (r = 0.229; ns) increased with advancing age. There was a significantly negative correlation (r = -0.499; p less than 0.01) between CBF and the number of WMLs. While, CVR showed a positive correlation with the number of WMLs (r = 0.468; p less than 0.01). Multivariate regression analysis with stepwise forward selection method indicated that the number of WMLs and age were independent and negative predictors for CBF, while other factors did not. CBF decreased with a concomitant rise in CVR. On the basis of the results listed above, we assumed that ischemic damage of the white matter and/or functional suppression of distant loci due to the primary tissue damage are the best explanation for CBF reduction in asymptomatic individuals with WMLs. High resolution CBF imaging as well as evaluation of structural alterations in cerebrovascular vessels should be required to further define the mechanisms.

Adult↗
PubMed1990

Platelet production, clearance and distribution in patients with idiopathic thrombocytopenic purpura.

Platelet destruction mechanism was thought to play a primary role in autoimmune thrombocytopenia (ITP). There is, however, some evidence that anti-platelet antibodies in ITP impair megakaryocytopoiesis. Using autologous In-111 platelets, we tried to elucidate this point. We measured platelet survival, platelet turnover, platelet sequestration sites, and platelet production (turnover) to the clearance (sum of liver and spleen platelet uptake) ratio in 8 normal subjects and 12 patients with ITP whose platelet counts ranged from 9 x 10(9) to 40 x 10(9)/L. The sum of platelet uptake in the liver and spleen showed a significant inverse correlation with platelet survival. Platelet survival, platelet production to clearance ratio correlated significantly with the platelet count. No significant correlation was found between platelet turnover and platelet counts. The distribution of platelet turnover showed considerable individual variation; 8 of 12 patients showed platelet turnovers which were lower than the normal value, but the others were within the normal range. We concluded that although the platelet destruction mechanism in the reticuloendothelial system shows a primary role in thrombocytopenia, the impaired rate of effective thrombopoiesis may also contribute to the severity of ITP.

Adult↗
PubMed1990

27 amino acid residues can be deleted from the N-terminus of human lymphotoxin without impairment of its cytotoxic activity.

In order to study the relationship between activity and structure of human lymphotoxin (hLT, 171 aa), we synthesized the gene (519 bp) for hLT and expressed it in Escherichia coli. Purification of the recombinant hLT from crude extracts was difficult because of the low level of expression of the gene. To improve the yield of the recombinant protein, we prepared five truncated genes for mutant proteins in which 25, 26, 27, 28 and 37 amino acid residues, respectively, were missing from the N-terminus. All of the genes were efficiently expressed and adequate amounts of mutant proteins were synthesized. The proteins were recovered mainly in the supernatant fractions after disruption of cells, with the exception of LT delta 37N, in which 37 residues were absent from the N-terminal region. Cytotoxic activities against mouse fibroblast L929 cells were detected in supernatant fractions that contained these mutant proteins, except in the case of LT delta 28N, which lacks the first amino acid residue conserved in both hLT and human tumour necrosis factor (hTNF). LT delta 27N, which is the smallest of the active proteins, was purified to homogeneity, and its cytotoxic activity was found to be similar to that of recombinant hTNF.

Amino Acid Sequence↗
PubMed1990

Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death.

We investigated the pathogenic role of free radical formation in ischemic neuronal death using radical scavenger, superoxide dismutase. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. The effects of free superoxide dismutase and a derivatized superoxide dismutase, pyran copolymer conjugated superoxide dismutase, on early ischemic damages, detected sensitively by the immunohistochemical reaction for microtubule associated protein 2, and a subsequent delayed neuronal death after restoration of blood flow were investigated. Preischemic treatment by pyran conjugated superoxide dismutase showed clear protective effects against both the neuronal damages detected by immunohistochemistry after 5 min ischemia and the delayed neuronal necrosis after one week of recovery, although no clear beneficial effects were observed when this drug was administered just before the recirculation or free superoxide dismutase was used. These results strongly suggest that free radical generation during brief period of ischemia plays a pivotal role in triggering the ischemic neuronal damages causing delayed neuronal death at the selectively vulnerable areas of the brain.

Animals↗
PubMed1990

[Functional alterations of human platelets following 111In labeling with different ligands and incubation media].

We studied the effects of various 111In-water soluble chelates and incubation media on labeling efficiency of platelets and in vitro platelet aggregability. High labeling efficiency of platelets in ACD-saline was achieved with 111In-oxine sulfate, 111In-tropolone and 111In-MPO (2-mercaptopyridine-N-oxide). In the condition with 4.8 x 10(6)/mm3 platelets in ACD-plasma, 111In-oxine-sulfate had low labeling efficiency and inconsistent labeling, while 111In-tropolone and 111In-MPO had high labeling efficiency. In vitro platelet aggregability (ADP 2 microM) was reduced when platelets were labeled in the absence of plasma. However, there was no significant difference in platelet aggregability among 111In-platelets labeled by three different chelates. In conclusion, to maintain aggregation activity of the platelets with relatively high labeling efficiency, the best result was obtained by using MPO or tropolone chelate in plasma at 4.8 x 10(6)/microliters platelet concentration.

Adult↗
PubMed1990

[Platelet production, clearance and distribution in patients with idiopathic thrombocytopenic purpura].

We have studied 8 normal subjects, and 12 patients with idiopathic thrombocytopenic purpura whose platelet counts ranged from 9 x 10(9)/L to 40 x 10(9)/L. Autologous platelets labeled with 111Intropolone were used for evaluation of mean platelet survival, platelet turnover, platelet sequestration sites, and platelet production (turnover) to clearance (sum of platelet uptake in the liver and the spleen) ratio. Platelet survival correlated directly with platelet counts. There was no significant correlation between the platelet sequestration pattern and platelet count, survival, or turnover. Sum of platelet uptake in the liver and the spleen showed a significant inverse correlation with platelet survival. No significant correlation was found between platelet turnover and platelet count. There was a significant correlation between the platelet production to clearance index when all subjects were analyzed. The distribution of platelet turnover showed considerable individual variation; eight of twelve patients showed platelet turnover less than mean minus 2SD of the control value, but others showed normal range. We conclude that although platelet destruction mechanism in RES shows a primary role of thrombocytopenia, impaired rate of effective thrombopoiesis may also contribute to disease severity in ITP.

Adult↗
PubMed1990

A new apparatus for brain imaging: four-head rotating gamma camera single-photon emission computed tomograph.

The development of a new rotating gamma camera SPECT device for imaging the brain was undertaken with the objective of achieving the highest full volume imaging spatial and temporal resolution performance. For this purpose, four rectangular gamma camera detectors were arranged as close to the head as possible, and united in a block to insure detector head registration and alignment as well as to enable rotation stability at high speeds. Phantom and clinical studies performed demonstrated 42 sequential, 4-mm thick transaxial images acquired in one scan and with sufficient volume to permit the entire cerebrum and cerebellum to be imaged with high sensitivity. The central field of view reconstructed spatial resolution measured 7.0 mm full width of half maximum utilizing the high-resolution collimator, and tomographic images of arbitrary planes including sagittal and coronal demonstrated equally high resolution. The high sensitivity and high speed rotational acquisition capability of the device permits dynamic SPECT studies to be carried out in the analysis of rapidly varying radiotracer concentrations.

Brain↗
PubMed1989

Platelet aggregability and in vivo platelet deposition in patients with ischemic cerebrovascular disease--evaluation by indium-111-platelet scintigraphy.

In ischemic cerebrovascular disease, it is not clear whether platelet function in vitro actually reflects the situation in vivo. Using indium-111 platelet scintigraphy as a method for detecting platelet activation in vivo, we tried to elucidate this problem. Twenty eight patients with chronic stage of ischemic cerebrovascular disease (CVD) and 17 control subjects were examined. Platelet scintigrams were positive in 9 of 28 patients in CVD, while all were negative in control. A comparison of the results obtained from qualitative platelet imaging and platelet aggregability was performed to evaluate whether threshold aggregation concentration (TAC) grade differed across the three groups (control, CVD patients without platelet deposition and CVD patients with platelet deposition). CVD patients with platelet deposition showed a higher TAC than those patients who did not show platelet deposition (P less than 0.05) or control subjects without platelet deposition (P less than 0.05). These results suggest that some patients in chronic stages of CVD may have active platelet deposition on carotid atheromatous lesions, and presence of platelet deposition in vivo could contribute to reduce platelet reactivity in peripheral blood.

Adult↗
PubMed1989

Prediction of stroke-prone gerbils and their cerebral circulation.

We attempted to predict the severity of cerebral ischemia, prior to permanent occlusion of a common carotid artery (CCA), in the gerbil by measuring the diameter of the distal CCA before and during temporary ligation and correlated the severity of cerebral ischemia and the pattern of cerebral circulation. All gerbils with reduction of the diameter over 44% after temporary occlusion developed severe neurological signs following permanent ligation. These gerbils lacked any connection between the left and right anterior cerebral arteries (ACA) and the pericallosal arteries originated from the ACA of the occluded side. No gerbils with reduction of less than 30% developed neurological signs and those gerbils possessed a definite anastomosis between the ACAs from both sides. Six of 7 gerbils without connection between the ACAs whose pericallosal arteries originated from the ACA of the non-occluded side proved to be moderately symptomatic. It was concluded that we could reliably predict severely symptomatic and moderately symptomatic gerbils with specific cerebral circulation patterns prior to permanent occlusion of the CCA. The preselected 'stroke-prone' gerbils should be useful for the investigation of cerebral ischemia and the evaluation of pharmacological agents.

Animals↗
PubMed1989

Microtubule-associated protein 2 as a sensitive marker for cerebral ischemic damage--immunohistochemical investigation of dendritic damage.

We investigated the neuronal distribution of microtubule-associated protein 2 in gerbil brain and monitored the progression of ischemic damage immunohistochemically by using this protein as a dendritic marker. The reaction for microtubule-associated protein 2 in normal gerbil brain clearly visualized neuronal soma and dendrites but other structures such as axonal bundles, glia and endothelial cells exhibited little immunoreactivity. In a reproducible gerbil model of unilateral cerebral ischemia, we could detect the ischemic lesions as early as 3 min after right common carotid occlusion at the subiculum-CA1 region of the ipsilateral hippocampus as faint loss of the reaction in the dendrites. After ischemia for 30 min, the ischemic lesions were clearly detected as loss of the reaction in the nerve cell bodies, dendrites and the neuropil in the hippocampus, cerebral cortex, thalamus and the caudoputamen. Although the mechanism for prompt disappearance of the immunohistochemical reaction for microtubule-associated protein 2 is not clear, the present investigation suggests that dendrites in the vulnerable regions may be quite susceptible to ischemic stress and that the immunohistochemical procedure for microtubule-associated protein 2 may be very useful for demonstration of dendritic damage in various pathophysiological states of the central nervous system.

Animals↗
PubMed1988

Iodine-131-labeled fibronectin: potential agent for imaging atherosclerotic lesion and thrombus.

Fibronectin is known to interact with fibrin, collagen, etc. We have labeled fibronectin with 131I, and measured its accumulation in the deendothelialized lesion in the rabbit aorta to evaluate it as a candidate for imaging atherosclerotic lesions and thrombi. Accumulation of [131I] fibronectin in the deendothelialized lesion was apparent at 48 hr, and increased at 72 hr after injection of the agent. Our results indicate that radiolabeled fibronectin may be a useful tracer for imaging early atherosclerotic lesion and thrombus.

Animals↗
PubMed1987

A gamma camera system for atraumatic rCBF measurement using a new super high sensitivity collimator.

The purpose of this study is to develop a useful gamma camera system for atraumatic rCBF measurement by the 133Xe intravenous injection (i.v.) method. A super high sensitivity slant hole (SHS-SL) collimator was designed for this purpose. The gamma camera used with this collimator was able to move close to the patient's head and obtain satisfactory count rates (130 kcpm-178 kcpm in a hemisphere) with a low dosage (10 mCi) of 133Xe. To validate this rCBF measurement system three studies were carried out: a comparative evaluation was performed against the flow values with the intracarotid 133Xe injection (i.c.) method, reproducibility of flow values was assessed from two serial i.v. measurements, and flow values were compared with clinical severity of the patients. The comparative study showed good correlation in the hemispheric and regional values between the two methods; r values 0.98 and 0.64-0.93 for gray matter flow and 0.96 and 0.78-0.93 for initial slope index. In the reproducibility study, the variation coefficients in the hemispheric and regional values between the two serial measurements were 5.0% and 7.3%-14.2% for gray mater flow, 5.2% and 7.9%-12.9% for initial slope index. The reproducibility in this study was as good as those with the i.c. method reported previously. The hemispheric flow values from our gamma camera system correlated well with the clinical severity of cerebrovascular disease. These results show that the gamma camera system with the SHS-SL collimator is useful for atraumatic rCBF measurement.

Brain Ischemia↗
PubMed1987

Binding of 131I-labeled tissue-type plasminogen activator on de-endothelialized lesions in rabbits.

Tissue-type plasminogen activator (t-PA) which has a high affinity for fibrin in the clot, was labeled with 131I by the iodogen method, and its binding to de-endothelialized lesions in the rabbit was measured to assess the detectability of thrombi. The de-endothelialized lesion was induced in the abdominal aorta with a Fogarty 4F balloon catheter. Two hours after the de-endothelialization, 131I-labeled t-PA (125 +/- 46 microCi) was injected intravenously. The initial half-life of the agent in blood (n = 12) was 2.9 +/- 0.4 min. The degree of binding of 131I-labeled t-PA to the de-endothelialized lesion was evaluated at 15 min (n = 6) or at 30 min (n = 6) after injection of the agent. In spite of the retention of the biochemical properties of 131I-labeled t-PA and the presence of fibrin deposition at the de-endothelialized lesion, the binding of t-PA to the lesion was not sufficiently strong. Lesion-to-control ratios (cpm/g/cpm/g) were 1.65 +/- 0.40 (at 15 min) and 1.39 +/- 1.31 (at 30 min), and lesion-to-blood ratios were 1.39 +/- 0.32 (at 15 min) and 1.36 +/- 0.23 (at 30 min). These results suggest that radiolabeled t-PA may be inappropriate as a radiopharmaceutical for the scintigraphic detection of a pre-existing thrombotic lesion.

Animals↗
PubMed1986

Imaging platelet deposition on Dacron bifurcation grafts in man: quantification by a dual-tracer method using 111In-labeled platelets and 99mTc-labeled human serum albumin.

A dual tracer technique using 111In-labeled platelets and 99mTc-labeled human serum albumin was applied to evaluate the thrombogenicity of Dacron bifurcation arterial grafts. The level of platelet accumulation over the whole of the graft was estimated from the ratio of 111In-platelet radioactivity deposited on the vascular wall to these radioactivity circulating in the blood pool, i.e., the platelet-accumulation index (PAI). Furthermore, the PAI value was calculated for each pixel in digitized images and the PAI distribution image (PAI image) was reconstructed. Eighteen patients with DeBakey knitted Dacron bifurcation grafts and 11 normal volunteers were studied. Of the 18 patients, 11 had no graft occlusion (group I) and the remaining 7 (group II) had occlusion. The mean PAI value (+/- SD) over the whole of the graft in group I was 32.6% +/- 33.7% as compared to -8.8% +/- 4.5% in the control group (P less than 0.01). In group I, the PAI value over the entire graft decreased with the age of the graft (r = -0.763; P less than 0.01). In contrast, in group II, platelet accumulation did not diminish with time and persisted beyond the time of which platelet accumulation was no longer found in group I. Moreover, analysis of the PAI images revealed enhanced platelet accumulation on the proximal part of the graft to be more frequent in group II than in group I (6/7 vs 0/11; chi 2c = 10.55; P less than 0.005). The method used for platelet imaging in the present study may be useful in the study of platelet reactions on Dacron arterial prostheses.

Aged↗