Hideo Shio

Quantitative Comparison of the Bolus and Steady-State Methods for Measurement of Cerebral Perfusion and Oxygen Metabolism: Positron Emission Tomography Study Using 15O-Gas and Water

To evaluate a new simplified bolus method for measurement of cerebral perfusion and metabolism, the parametric images with that method were compared with those obtained from the conventional steady-state method with 15O-gas. The new method also provided images of arterial blood volume (V0), which is a different parameter from cerebral blood volume (CBV) obtained using a C15O technique. Seven healthy volunteers and 10 patients with occlusive cerebrovascular diseases underwent positron emission tomography (PET) scans with both methods. Three-weighted integration was applied to calculate regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) in the bolus method. Global and regional CBF and CMRO2 in volunteers were compared between the two methods and used as control data. Regional values in patients also were evaluated to observe differences between the bilateral hemispheres. Both rCBF and rCMRO2 were linearly well correlated between the two methods, although global difference in CMRO2 was significant. The difference in each parametric image except for V0 was significant between the bilateral hemispheres in patients. The bolus method can simplify oxygen metabolism studies and yield parametric images comparable with those with the steady-state method, and can allow for evaluation of V0 simultaneously. Increase in CBV without a change in V0 suggested the increase might mainly be caused by venous dilatation in the ischemic regions.

Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease

OBJECTIVES The loss of the neurons in layer 3, one of the groups of cortical neurons most vulnerable in various degenerative brain diseases, results in axonal degeneration leading to atrophy of the corpus callosum. Previous studies showed callosal atrophy in three degenerative dementias: frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimers disease (AD). However, it is unclear whether a characteristic pattern of atrophy is present in each. The objective of this study was to investigate whether the pattern of the callosal atrophy was different among patients with FTD, PSP, or early onset AD. METHODS Eleven patients with FTD, nine patients with PSP, 16 patients with early onset AD, and 23 normal controls, all age and sex matched, were studied using MRI. The ratios of midsagittal corpus callosum areas to the midline internal skull surface area on T1 weighted images were analyzed. The corpus callosum was divided into quarters: the anterior, middle-anterior, middle-posterior, and posterior portions. RESULTS Compared with controls, all three patient groups had significantly decreased total callosal/skull area ratio. An analysis of covariance adjusted for the total callosal area/skull area ratio showed that the anterior quarter callosal/skull area ratio in FTD, the middle-anterior quarter area ratio in PSP, and the posterior quarter area ratio in AD were significantly smaller than those in the other three groups. CONCLUSION Although atrophy of the corpus callosum is not specific to any degenerative dementia, the patterns of the atrophy are different among patients with FTD, PSP, or early onset AD. Differential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia.

Corpus Callosum Atrophy in Patients With Leukoaraiosis May Indicate Global Cognitive Impairment

BACKGROUND AND PURPOSE The extent of white matter high-intensity lesions (WMLs) on T2-weighted MR images may be an indicator of cognitive impairment, especially impairment related to frontal lobe dysfunction. However, it is unclear whether the extent of WMLs is an independent predictor of cognitive impairment. In patients with extensive WMLs, atrophy of the corpus callosum may be an important predictor of global cognitive impairment. The purpose of this study was to investigate the relation of the extent of WMLs and callosal size with cognitive functions in a patient population with a wide range of extent of WMLs. METHODS We studied 62 patients, aged 49 to 86 years, who underwent MRI because of neurological symptoms and were diagnosed as having lacunar stroke or no specific neurological disease: 28 with lacunar infarcts and 34 without. Multivariate analysis was used to test the independent predictive value of patient age, sex, educational level, other medical illness, lacunar infarct, corpus callosum area, and extent of WMLs with respect to scores of Mini-Mental State Examination or verbal fluency task. RESULTS Only callosal size and age were significant independent predictors of the scores of the Mini-Mental State Examination, while only the extent of WMLs was an independent predictor of the score of the verbal fluency task. CONCLUSIONS Callosal atrophy may be an important predictor of global cognitive impairment in patients with WMLs, whereas the extent of WMLs per se may be related to impairment of frontal lobe function independent of callosal atrophy.

Antithrombotic treatment in livedo vasculitis

Two patients with livedo vasculitis were treated successfully with antiplatelet drugs including ticlopidine hydrochloride, dipyridamole, and low-dose aspirin. Increased platelet functions were restored 1 week after the beginning of the treatment, followed by dramatic improvement of painful leg ulcers within 1 month. Livedo status was unchanged. We claim that antiplatelet therapy should be the first choice of treatment in this disease.

LTC4/LTB4 Alterations in Rat Forebrain Ischemia and Reperfusion and Effects of AA-861, CV-3988

LTC4, which enhances vascular permeability and promotes tissue edema, and LTB4, which is a potent chemotactic and activating factor for leukocytes, were measured in rat brain after ischemia and several time periods of reperfusion. Forebrain ischemia was induced by 4-vessel occlusion. LTC4/LTB4 in the brain were measured by RIA. We also studied the effects of a 5-lipoxygenase inhibitor, AA-861 and a PAF antagonist, CV-3988 on LTC4/LTB4 concentrations. LTC4 in brain tissue increased during 30 min forebrain ischemia (p < 0.001). After reperfusion, LTC4 increased further, but at 15 min reperfusion LTC4 returned to the control level. Tissue levels of LTB4 in the brain increased during 30 min ischemia and remained high until 5 min after reperfusion (p < 0.01) returning at 15 min reperfusion to the control level. AA-861 inhibited elevation of LTC4/LTB4 in the reperfusion phase, but was not effective during ischemia. CV-3988 had a similar effect. LTC4 and LTB4 may be involved in the pathogenesis of ischemia brain edema and leukocyte infiltration. Further, PAF and LTs have many similarities of their pathophysiological properties, and may interact therefore in pathologic process.

Atrophy of the corpus callosum associated with a decrease in cortical benzodiazepine receptor in large cerebral arterial occlusive diseases

OBJECTIVES It remains controversial whether selective neuronal ischaemic change develops in patients with occlusion of the large cerebral arteries. Previous studies have shown atrophy of the corpus callosum with reduced cortical oxygen metabolism in large cerebral arterial occlusive diseases, which might be indirect evidence of loss of the neurons in cortical layer 3. Recent studies of patients with ischaemic cerebrovascular diseases have demonstrated reduced central benzodiazepine receptor (BZR) binding in the normal appearing cortical areas, which might be more direct evidence of changes of the neurons. Although pathophysiology of the decreased BZR is unclear, a decrease in the cortical BZR binding with neuronal loss would cause atrophy of the corpus callosum. The purpose of this study was to determine whether atrophy of the corpus callosum is associated with a decrease in cortical BZR binding in large cerebral arterial occlusive diseases. METHODS Seven patients with occlusive diseases of the middle cerebral or internal carotid artery and only minor subcortical infarctions were studied. Single photon emission tomographic images of 123I labelled iomazenil (IMZ) obtained 180 minutes after injection were analysed for BZR binding. The midsagittal corpus callosum area/skull area ratio (on T1 weighted magnetic resonance images) was compared with the cerebral IMZ uptake/cerebellar IMZ uptake ratio. RESULTS Compared with 23 age and sex matched control subjects, the patients had significantly decreased callosal area/skull area ratio. The degree of corpus callosum atrophy was significantly and strongly (ρ=0.99, p<0.02) correlated with that of the decreases in the mean cerebral cortical IMZ uptake ratio. CONCLUSION Corpus callosum atrophy may occur in association with a decrease in cortical BZR binding in large cerebral arterial occlusive diseases. Corpus callosum atrophy with decreased cortical BZR binding might reflect cortical neuronal damage in large cerebral arterial occlusive diseases.

On the active principles in Toh's alkaline tissue extracts which cause release of serotonin from blood platelets

SummaryThe release of serotonin from rabbit blood platelets by the alkaline extracts of tissue, originally described byToh in 1956, was re-examined. The extracts were found not only to cause the release of serotonin on incubation with platelets, but also to inhibit strongly the uptake into platelets of the amine added to the incubation medium. Hardly any apparent damage of platelets was, however, caused by the extracts. The activity of the extracts was dependent on temperature and varied with the tissue used. Extracts of kidney showed the greatest activity. Moreover, the activity was inhibited by the presence of glucose in the incubation medium but remained unaffected after pretreatment with trypsin and chymotrypsin.Based on these results, partial purification and chemical characterization of active principles in the alkaline kidney extract was attempted using extraction with organic solvents and thin-layer chromatography. The results obtained strongly suggest that the active principles are of acidic lipid nature and it is highly probable that they are mono- and di-enoic fatty acids set free by the alkali treatment used for tissue extraction. Such a view was supported by a model experiment in which authentic oleic and linoleic acid could liberate platelet serotonin on incubation but stearic and linolenic acid failed to do so.

Scanning electron microscopy studies of erythrocytes in spinocerebellar degeneration.

Spinocerebellar degeneration is a heredofamilial disease of unknown aetiology. The shape of erythrocytes as revealed by scanning electron microscopy was studied in this disease. Echinocytes I, as defined by Bessis, were seen more frequently in spinocerebellar degeneration than in age and sex matched controls (7.2 +/- 1.5% in spinocerebellar degeneration, 3.4 +/- 1.2% in controls, p less than 0.001), Parkinsons disease, motor neuron disease, myopathy, and Huntingtons chorea. Erythrocyte deformability was impaired to a greater extent in spinocerebellar degeneration than in the controls when the pH was raised from 7.2 to 8.0; Echinocytes I in spinocerebellar degeneration increased from 8.4 +/- 0.6 to 15.4 +/- 2.4%, in the control group from 2.8 +/- 1.2 to 13.3 +/- 2.1%. In spinocerebellar degeneration no significant correlation was found between the level of serum low density lipoprotein and the number of Echinocytes I. In both groups there was a significant correlation between the occurrence of Echinocytes I and age, and the difference of Echinocytes I was greater in aged subjects in spinocerebellar degeneration. The data suggest that membrane abnormality in erythrocytes exists in spinocerebellar degeneration and may be accelerated with the advance of age.

Substance P and antistrychnine activity

SummaryThe administration to mice of crude substance P prepared from bovine brain inhibited strychnine convulsions. After alumina column chromatography, this antistrychnine activity was observed mainly in the fraction which was not adsorbed, while those fractions containing substance P or its satellite polypeptides (Zetler, 1963) were found ineffective. The regional distribution of such an antistrychnine activity in bovine brain was also found to be different from that of substance P. Experiments in which inactivation with proteases and dialysis were investigated suggested that the component or components bearing the antistrychine activity were of a polypeptide nature.

Mode of action on the platelet 5-HT of the active principles in Toh's alkaline tissue extract.

Summary1.The serotonin (5-HT)-releasing action of active components partially purified from Tohs alkali kidney extract was studied by incubation with rabbit blood platelets.2.The 5-HT release caused by the active components was shown to be practically un-affected by the pH (6.5–8.0) of the incubation media and was independent of the presence of Ca2+. The 5-HT release was negligible at lower temperatures (less than 30° C), an obvious release being observed only at 37° C. In the presence of glucose in the incubation medium, 5-HT liberation was depressed even with a glucose concentration as low as 1 μM. There was a stoichiometric relation between the platelet count and the dose of the extract; as long as the ratio of these two terms was fixed, the extent of 5-HT release could be kept nearly constant. The inhibitory effect of glucose was competitive.3.The active components seemed to suppress the amine influx into platelets incubated at 37° C, with14C-5-HT for 60 min but scarcely affected the influx at 20° C or 0° C. Glucose antogonised this inhibitory action of the extract. The findings suggest that the passive 5-HT exchange was not altered by the extract, but active amine uptake was affected.