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Biomedical subjects

N Handa

Publications and source records attributed to N Handa.

At least 109 records · Page 6Linked to original sources

Formation and morphology of helical structures from phospholipid-ribonucleoside conjugates in an acidic solution.

Phospholipid-ribonucleoside conjugates containing two myristoyl groups and a ribonucleotidyl group, dimyristoyl-5'-phosphatidyl-ribonucleosides, have been synthesized, and their self-organization and morphology have been investigated in acidic solutions. In acidic solutions, dimyristoyl-5'-phosphatidyl-ribonucleosides produced much different helical structures from those produced in neutral and alkaline solutions.

Hydrogen-Ion Concentration↗

'Ischemic tolerance' phenomenon found in the brain.

We investigated the possibility that neuronal cells given a mild ischemic treatment sufficient to perturb the cellular metabolism acquired tolerance to a subsequent, and what would be lethal, ischemic stress in vivo. Cerebral ischemia was produced in the gerbils by occlusion of both common carotids for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. Minor 2-min ischemia in this model depletes high-energy phosphate compounds and perturbs the protein synthesis, but never causes neuronal necrosis, and therefore was chosen as mild ischemic treatment. Single 2-min ischemia 1 day or 2 days before 5 min ischemia exhibited only partial protective effects against delayed neuronal death. However, two 2-min ischemic treatments at 1 day intervals 2 days before 5 min ischemia exhibited drastically complete protection against neuronal death. The duration and intervals of ischemic treatment, enough to perturb cellular metabolism and cause protein synthesis, were needed respectively, because neither 1-min ischemia nor 2-min ischemia received twice at short intervals exhibited protective effects. This 'ischemic tolerance' phenomenon induced by ischemic stress--which is unquestionably important--and frequent stress in clinical medicine, is intriguing and may open a new approach to investigate the pathophysiology of ischemic neuronal damage.

Animals↗

A validation study on the reproducibility of transcranial Doppler velocimetry.

The transcranial Doppler method for the measurement of intracranial arterial blood flow velocity is a useful noninvasive technique with a number of applications. The present study validated the reproducibility of this method for repeated measurements of flow velocity in the middle cerebral and basilar arteries. Fifteen healthy volunteers were studied. Measurements were made twice by one examiner and once by another in a single day and again by the first examiner on another day. The reproducibility was evaluated by calculating the correlation coefficient (r) and the coefficient of variation (CV) of the difference between the values obtained from each pair of measurements. Although depending on the examiner, the time interval between the examinations and the vessels studied some differences were noted in the reproducibility, both the r (0.69-0.95) and CV (6.7%-19.5%) values in the whole study were good enough to warrant the applicability of this method for the repeated measurements of the intracranial arterial blood flow velocity in future studies.

Cerebral Arteries↗

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↗

Ultrasonic evaluation of early carotid atherosclerosis.

We investigated the prevalence of carotid atherosclerosis, including mild early lesions, and its association with cervical bruits and various risk factors (age, male sex, hypertension, hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking) in 232 consecutive Japanese patients. High-resolution real-time B-mode ultrasonography was performed to determine the extent of atherosclerosis, and it was quantified by using a scoring system. The prevalence of carotid atherosclerosis was 49%, 59%, and 41% in all 232 patients, the 100 symptomatic patients, and the 132 asymptomatic patients, respectively. Although carotid lesions were detected frequently (87%) in the 30 patients with cervical bruits, bruits were noted in only 30% of the 88 examined patients with carotid atherosclerosis. Independent risk factors for carotid atherosclerosis in these patients were found to be age, male sex, and hyperlipidemia; diabetes mellitus was a possible risk factor for carotid atherosclerosis. Our study did not show a close association between hypertension and carotid atherosclerosis, and this might be caused by the high prevalence of hypertension in our patients. Our findings suggest an increasing prevalence of carotid atherosclerosis in the Japanese, though this should be confirmed in a population-based study. Our study demonstrates the clinical usefulness of high-resolution B-mode ultrasonography for the evaluation of early carotid atherosclerosis.

Adult↗

Postlaminectomy ossified extradural pseudocyst. Case report.

A large ossified spurious meningocele accompanied by recurrent lumbar disc herniation occurred 7 years after posterior intervention for laminectomy and discectomy in a 53-year-old man. The cyst wall, histologically composed of mature bone tissue, was sparsely covered with connective tissue and lined with fibrocyte- or fibroblast-like cells on the inside. The ossified pseudocyst was presumed to have originated from a minute defect in the dura mater which occurred at the time of the first operation.

Calcinosis↗

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↗

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↗

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↗

Levallorphan and dynorphin improve motor dysfunction in Mongolian gerbils with unilateral carotid occlusion: the first application of the inclined plane method in the experimental cerebral ischemia.

Levallorphan and dynorphin were effective on the motor dysfunction in the gerbil model of unilateral cerebral ischemia. The effect of opioids, levallorphan (mixed agonist-antagonist), dynorphin (kappa-receptor agonist) and naloxone (mu-receptor antagonist), on neurological impairment was evaluated using the unilateral cerebral ischemia model of gerbil. Motor function was evaluated quantitatively by using the inclined plane method. Both levallorphan-treated group and dynorphin-treated group showed a significant improvement of the motor dysfunction compared with saline-control group. On the other hand, naloxone-treated group did not differ from saline-control group. The beneficial effect of these opioids on motor dysfunction might be mediated by the kappa-opioid receptor. This study also showed the potential usefulness of the inclined plane method for the investigation on the cerebral ischemia.

Animals↗

Carbondioxide reactivity of the blood flow in human basilar artery estimated by the transcranial Doppler method in normal men: a comparison with that of the middle cerebral artery.

Using the transcranial Doppler technique, the carbondioxide reactivity of the blood flow velocity in the human basilar artery (BA) was investigated in healthy volunteers for comparison with that in the middle cerebral artery (MCA). An exponential curve with an exponent of 0.044 mmHg-1 was found to be a good fit to the BA data and 0.040 mmHg-1 to the MCA data, respectively. While the response of both arteries showed a good correlation to the end-tidal carbondioxide partial pressure (PETCO2), there was no significant difference observed between the carbondioxide (CO2) reactivity of each artery. In both arteries, the end-diastolic flow velocity decreased significantly with the reduction of PETCO2, which may represent the increasing resistance of cerebral microvasculature in hypocapnia. Because of the reliability and noninvasiveness of this method, this normal value should be quite helpful for the bed-side evaluation of an altered CO2 response in the patients with cerebrovascular disease.

Adult↗

Efficacy of echo-Doppler examination for the evaluation of renovascular disease.

The accuracy of the diagnosis of renal artery stenosis using noninvasive echo-Doppler velocimetry was compared with that of angiography in 40 renal arteries. The duplex-Doppler signals were detected through the muscle of the back (the translumbar approach). Renal artery stenosis was diagnosed by three objectively defined Doppler parameters, the acceleration index (AI), the acceleration time (AT), and the acceleration time ratio (ATR). The normal range obtained on 11 control subjects was defined as AI greater than or equal to 3.78, AT less than or equal to 0.07 s, and ATR less than or equal to 1.35. High technological success (98%) was obtained using the translumbar approach. In comparison with angiography (cases of significant stenosis), the accuracy of the echo-Doppler method using the criteria of the AI was 95%, the sensitivity was 100%, and the specificity was 93%. This noninvasive method may be one of the most accurate screening methods for diagnosing significant renal artery stenosis.

Blood Flow Velocity↗

A new accurate and non-invasive screening method for renovascular hypertension: the renal artery Doppler technique.

The clinical use of ultrasonic echo Doppler velocimetry as a screening test for renal artery stenosis was investigated in 11 control subjects and 20 hypertensive patients including 10 with renovascular disease. In these hypertensive patients, the accuracy of the diagnosis of renal artery stenosis using the echo Doppler method was compared with that of angiography. The accuracy of the radionuclide renography in the same subjects was also investigated and compared with that of the echo Doppler method. Seven patients with renovascular disease who required angioplasty were examined again after the operation. The duplex Doppler signals were detected through the muscle of the back (the translumbar approach). Diagnosis of renal artery stenosis was based on three objectively defined Doppler parameters, the acceleration index, the acceleration time, and the acceleration:time ratio. In comparison with angiography, the accuracy of the echo Doppler method evaluated by using these parameters was 95%; the sensitivity was 100% and the specificity was 93%. The accuracy of the ultrasonic study was superior to that of radionuclide renography (80%). The acceleration index of the affected side was significantly correlated with the percentage stenosis of the renal artery. The changes in renal arterial blood flow following the operation were detected well by the Doppler parameters. This non-invasive method is one of the most accurate screening tests available for renovascular hypertension and has also proved quite useful for follow-up examinations in the patients with angioplasty.

Blood Flow Velocity↗

Zinc status and its relations to growth retardation in children with biliary atresia.

Zinc status was studied in 36 children with biliary atresia and in ten children with Hirschsprung's disease or anorectal anomalies. Changes in preoperative and postoperative plasma and urinary zinc levels were measured in 16 children with biliary atresia and ten children with Hirschsprung's disease or anorectal anomalies. Hypozincemia was evident in children with biliary atresia preoperatively and became severe with time when adequate zinc supplementation was not given. Follow-up studies were done in 20 children with biliary atresia aged between 9 months to 10 years. The children with poor bile excretion and impaired liver function tended to have hypozincemia and a high excretion of zinc. Growth retardation was also common in these children. Careful monitoring and appropriate supplementation of micronutrients, including zinc is probably important for normal growth in children with biliary atresia.

Biliary Atresia↗

Carbohydrate metabolism in infants with biliary atresia.

Carbohydrate metabolism in 9 infants with biliary atresia (BA) was investigated preoperatively and during the early postoperative period when these infants were on parenteral nutrition for 7 days. Findings were compared with data on infants without liver dysfunction. Changes of plasma glucose, immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) in the biliary atresia group with moderate liver fibrosis were the same as those in the control group. However, in one patient with marked liver fibrosis, the molar IRI/CPR ratio was significantly low, thereby suggesting an increased hepatic insulin extraction. This change, however, was transient and the molar IRI/CPR ratio gradually returned to the level of other BA patients and the control groups after the 1st postoperative day. This study shows that in infants with BA, the glucose intolerance seen in adults with obstructive jaundice is absent and the parenteral nutrition can be performed without severe changes of carbohydrate metabolism.

Biliary Atresia↗

Echo-Doppler velocimeter in the diagnosis of hypertensive patients: the renal artery Doppler technique.

The renal blood flow velocity characteristics in 8 normal controls, 19 essential hypertensive patients and 8 hypertensive patients with renovascular disease were evaluated using echo-Doppler velocimetry. Two different approaches for ultrasonic detection of the renal artery, the translumbar and the transabdominal approach, were used. Renal Doppler sonograms were analyzed by measuring the acceleration index and the peak-systolic frequency/end-diastolic frequency (S/D) ratio. Renovascular patients who required surgery were examined before and after angioplasty. Doppler signals could be detected in all 35 subjects by using the translumbar approach. The acceleration index of the affected renal arteries significantly correlated to the percent stenosis of the renal artery determined by angiography. The acceleration index in the affected renal artery was improved by surgical treatment. The S/D ratio in essential hypertensives was significantly higher than that in the normal controls. There was a significant inverse correlation between the S/D ratio and creatinine clearance. Echo-Doppler velocimetry is considered to be useful in the diagnosis of renovascular disease and also in the evaluation of abnormalities of renal vascular resistance in hypertensive patients.

Adolescent↗

State of systemic hemodynamics in a case of juxtaglomerular cell tumor.

A renin-producing juxtaglomerular cell tumor was found in a 27 year-old woman. The infusion of angiotensin II analogue produced a marked decrease in arterial pressure. Oral administration of captopril also reduced her blood pressure. Although the renal vein renin did not indicate the laterality of the tumor, unilateral partial nephrectomy cured the disease. This is the first case report to describe measurement of several hemodynamic parameters before and after surgical removal of a juxtaglomerular cell tumor.

Adult↗