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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 667 records · Page 37Linked to original sources

[The effect of glycerol on regional cerebral blood flow, blood volume and oxygen metabolism].

Using positron emission tomography with 15O-labelled CO2 O2 and CO gases, the effects of glycerol on regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolism (CMRO2) were investigated in 6 patients with meningioma accompanying peritumoral brain edema. The same study was done in 5 normal volunteers. The changes of blood gases, hematocrit and hemoglobin were also examined. After a drip infusion of glycerol, the regional CBF increased not only in the peritumoral cortex and white matter but also in the intact cortex and white matter on the contralateral side. The increase of CBF was extensive and substantially there were no regional differences. In contrast, the changes of CMRO2 were not significant. This was derived from the increase in oxygen extraction fraction throughout extensive areas including the peritumoral area. There were no changes in CBV. Hematocrit and hemoglobin decreased to a small degree. In the normal volunteers, the same findings were noted. Thus, glycerol increases the functional reserve for cerebral oxygen metabolism, not only in the peritumoral regions but also in the intact regions. The effects of glycerol on hemodynamics and metabolism were discussed with reference to some differences from mannitol.

Adult↗

Effect of urinary trypsin inhibitor on osteoarthritis.

The plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in synovial fluid (SF) of osteoarthritis (OA) were examined to clarify their pathophysiological roles in this disease. Three PAs with molecular weights of 90K, 55K, and 33K were found in the SF, but the 55K PA was dominant. Immunologically, both the 55K and 33K PA were u-PA, while the 90K PA was t-PA. The PAI reacted against both u-PA and t-PA, but the PAI activity against u-PA was much stronger. Urinary trypsin inhibitor (UTI) made a complex with the 55K PA and suppressed the PA activity. A clinical study in which UTI was injected into the joint space of OA (18 joints in 15 patients) revealed excellent (39%), good (16%), and fair (44%) results based on assessment of the pain, range of motion, ballottement and activity of daily living.

Aged↗

Augmentation of tumor targeting in a line of glioma-specific mouse cytotoxic T-lymphocytes by retroviral expression of mouse gamma-interferon complementary DNA.

As an initial approach to experiments directed toward effective adoptive immunotherapy for cancer using lymphokine genes, we transferred retrovirally a complementary DNA encoding mouse gamma-interferon (IFN-gamma) into a specific cytotoxic T-lymphocyte clone, designated E-4, against 203 glioma cells (a 20-methylcholanthrene-induced mouse glioma line) and confirmed the efficacy of IFN-gamma production from the exogenous gene on augmentation of tumor targeting. Of five, two gene-transferred subclones constitutively produced 8 to 10 times the amount of IFN-gamma as compared with the parental E-4. Correspondingly, these two subclones exhibited 2 to 3 times higher killing activity against 203 glioma than the parental cells; the enhancement of the killing activities was abrogated by an adequate addition of anti-IFN-gamma antibody. No alteration was seen after the gene transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+,3+, and asialo-GM1-. The surface expression of a major histocompatibility complex Class I antigen, H-2Kb, was not altered remarkably, but the Class II antigen, I-Ab, was partially and slightly enhanced on the two IFN-gamma-producing sublines mentioned above on fluorescence-activated cell sorter analysis. Since it is considered that in the vicinity of the constitutively IFN-gamma producing cytotoxic T-lymphocyte cells tumor cells are exposed to a high concentration of IFN-gamma, the cells may be stimulated to induce or enhance the expression of surface antigens including major histocompatibility complex antigens as well as tumor-associated antigens relevant to immune recognition. The 203 glioma cells pretreated with IFN-gamma were more efficiently killed by both the parental E-4 and the gene-transferred sublines. Taken together, the results suggested that the augmented specific tumor-killing activity of our gene-transferred cytotoxic T-lymphocytes was ascribed to the constitutive production of IFN-gamma derived from the exogenous gene.

Animals↗

Immunoregulatory effects of interleukin 2 and interferon on syngeneic murine malignant glioma-specific cytotoxic T-lymphocytes.

The effects of interleukin 2 (IL2) and interferon (IFN) on the generation and lytic activation of syngeneic murine malignant glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin, 203-glioma)-specific cytotoxic T-lymphocyte (G-CTL) were investigated. The surface marker analysis showed that G-CTLs from both intracranial and s.c. tumor-bearing mice were composed of thymectomy-resistant (mature) Lyt-1-.2.3+ and thymectomy-sensitive (immature) Lyt-1+.2.3+ CTLs, which markedly decreased concurrently with increased intracranial pressure. G-CTLs were confirmed to be activated with target specificity by both factors in a different way. The CTL activation by IL2 (20 units/ml) remained for a longer time, although a lag time of 5 days after initial culture was required. IL2 influenced Lyt-1+.2.3+ CTLs to proliferate and develop the lytic potential. In contrast, even a 3-h incubation with IFN (1000 units/ml) could enhance the cytotoxicity, but the augmenting effects were observed no longer than 5 days later. IFN activated Lyt-1-.2.3+ CTLs and increased their proportion of the total cell population with a simultaneous decrease of Lyt-1+.2.3+ CTLs. Therefore, it was suggested that IL2 may provide a growth of CTL populations and that IFN can accelerate recruitment of new effectors, causing activation of the lytic process.

Animals↗

Possible origins of cerebrovascular nerve fibers showing vasoactive intestinal polypeptide-like immunoreactivity: an immunohistochemical study in the dog.

Changes of vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) in perivascular nerve fibers of the major cerebral arteries were examined immunohistochemically in the dog. The density of cerebrovascular nerve fibers showing VIP-LI (the average number of nerve fibers with VIP-LI in a unit area of the major cerebral arteries) was estimated, by using whole-mount preparations after extirpation of the pterygopalatine, otic or superior cervical ganglion. After pterygopalatine ganglionectomy, the density was markedly decreased in major cerebral arteries of both anterior circulation (the anterior cerebral and middle cerebral arteries) and posterior circulation (the basilar, superior cerebellar, posterior cerebral and posterior communicating arteries). After otic ganglionectomy, the density was moderately reduced in the major arteries of the posterior circulation, but was not decreased in those of the anterior circulation. After superior cervical ganglionectomy, the density was decreased markedly in the major cerebral arteries of the posterior circulation, and moderately in those of the anterior circulation. The results also indicate that the pterygopalatine, otic and superior cervical ganglia supply perivascular nerve fibers showing VIP-LI to the major cerebral arteries bilaterally with an ipsilateral dominance.

Animals↗

Automated determination of drugs in serum by column-switching high-performance liquid chromatography. II. Separation of theophylline and its metabolites.

The automated determination of theophylline and related compounds in human serum by column-switching high-performance liquid chromatography, including direct injection of serum samples, is described. TSK pre-column BSA-ODS and TSK gel ODS-80TM were used in the pre-column and analytical column, respectively. Serum samples of 20 microliters were directly injected on to the pre-column. After washing out serum proteins from the pre-column with 0.1 M NaH2PO4 at a flow-rate of 1.0 ml/min for 3.5 min, the effluent from the pre-column was introduced on to the analytical column by a column-switching device. The analysis was performed by stepwise gradient elution using 10 and 18% methanol in 0.1 M NaH2PO4. Theophylline and nine derivatives could be determined simultaneously within 40 min. The recovery of these compounds from serum was 95-103%. The linearity (1.0-50 micrograms/ml theophylline) and reproducibility (coefficient of variation less than 2.0%) were sufficient for drug monitoring at the lower and upper limits of therapeutic concentrations of theophylline.

Biotransformation↗

Cerebral circulation and oxygen metabolism in moyamoya disease of ischemic type in children.

Cerebral rCBF, rOEF, rCMRO2, and rCBV in moyamoya disease were studied by means of positron emmission tomography (PET), using 15O as a tracer. Steady-state methods with C15O2 and 15O2 were used to obtain the functional images of rCBF, rCMRO2, and rOEF. The 15O single-inhalation method was used to obtain the rCBV image. Five children (two boys and three girls) with mean age of 11 years and eight normal volunteers with mean age of 31 years were included in the study. The symptoms of moyamoya disease were due to cerebral ischemia, such as transient ischemic attack (TIA), reversible ischemic neurological deficit (RIND), and minor stroke. The interval between the latest ictus and PET scan ranged from 3 days to 3 years 6 months. Physiological parameters (rCBF, rCMRO2 etc.) in cerebral gray matter, cerebral white matter and basal ganglia were calculated from the single functional images. Any, low density areas appearing in X-ray-CT performed just prior to the PET study were carefully excluded from the analysis. The parameters of moyamoya disease were statistically compared with normal control parameters. Though the value of rCBF was slightly higher in moyamoya disease, this difference was not statistically significant. On the other hand, in moyamoya disease rCBV increased significantly in gray matter, white matter, and basal ganglia. The ratio of CBF to CBV is considered to be the index of perfusion pressure and reciprocal of cerebral mean transit time under the normal autoregulation of CBF. This ratio was calculated and compared with the normal value for each tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Two patients with meningioma visualized as high uptake by SPECT with N-isopropyl-p-iodo-amphetamine (I-123).

It has been reported that brain tumors show decreased IMP uptake, however, we encountered two cases of meningioma which had initially increased IMP uptake. SPECT was performed at 30 min, 2 hr and 6 hr after intravenous administration of IMP (3 mCi). The delayed images (2 and 6 h) showed decreased IMP uptake. These were convexity and parasagittal meningiomas which had tumor stains at angiography. Although the mechanism of IMP uptake in brain tumor is still unclear, this finding should be considered in the interpretation of IMP-SPECT.

Adult↗

Magnetic resonance imaging of cerebral infarction: time course of Gd-DTPA enhancement and CT comparison.

Thirty-five patients (7 females and 28 males) with cerebral infarction and suspicion of cerebral infarction of 4 h to 27 months duration were studied 45 times with magnetic resonance (MR) imaging using Gd-DTPA. Spin echo (SE) images were obtained before and after the administration of Gd-DTPA (0.1 or 0.15 mmol/kg) and compared with the enhanced CT. MR imaging using Gd-DTPA was more sensitive than enhanced CT and very useful for detecting a new focus of cerebral infarction, especially in the cases with multiple infarcted areas and for showing the extent of cortical and subcortical infarction. In most cases the MR enhancement was obvious in the subacute stage, especially after cerebral embolism, and the signal intensity of the lesion tended to show a gradual increase. The diagnosis of embolism was accepted on the basis of acute onset without prior TIA, coupled with angiography showing the embolus itself and/or a capillary blush and a wide area of infarction.

Adult↗

SPECT with [99mTc]-d,l-hexamethyl-propylene amine oxime (HM-PAO) compared with regional cerebral blood flow measured by PET: effects of linearization.

In order to validate the use of technetium-99m-d,l-hexamethylpropyleneamine oxime (HM-PAO) as a flow tracer, a total of 21 cases were studied with single photon emission computerized tomography (SPECT), and compared to regional cerebral blood flow (rCBF) measured by position emission tomography (PET) using the oxygen-15 CO2 inhalation technique. Although HM-PAO SPECT and rCBF PET images showed a similar distribution pattern the HM-PAO SPECT image showed less contrast between high and low activity flow regions than the rCBF image and a nonlinear relationship between HM-PAO activity and rCBF was shown. Based on the assumption of flow-dependent backdiffusion of HM-PAO from the brain, we applied a "linearization algorithm" to correct the HM-PAO SPECT images. The corrected HM-PAO SPECT images revealed a good linear correlation with rCBF (r = 0.901, p less than 0.001). The results indicated HM-PAO can be used as a flow tracer with SPECT after proper correction.

Adult↗

Primary brainstem death: a clinico-pathological study.

A case of primary brainstem death in a man with surgically treated cerebellar haemorrhage is reported. Necropsy revealed extensive necrosis confined to the brainstem and cerebellum. The absence of diabetes insipidus and the persistence of electroencephalographic activity were the characteristic clinical features of the case. This differentiates the condition from so-called "whole brain death". Analysis of three further cases with acute vascular lesions of the brainstem or cerebellum, shown at necropsy, revealed that primary brainstem death with prolonged somatic survival can occur in specific circumstances after surgical intervension.

Brain Death↗

Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats.

To elucidate the role of the internal elastic lamina in the development of cerebral aneurysm, the bifurcation of the anterior cerebral artery and olfactory artery was histologically studied in control and experimental rats treated with unilateral carotid ligation and renal hypertension. Various stages of aneurysm formation were compared, and it was found that early aneurysmal changes were always present just distal to the apical intimal pad on the anterior cerebral artery side. The internal elastic lamina was thinned and fragmented just distal to the pad even in the very early stage of aneurysm formation when the medial layer was still present. In control rats, the internal elastic lamina had a tendency to thin and fragment at the site where aneurysms would develop in experimental rats. Our study shows that changes of the internal elastic lamina were present just distal to the pad even in control rats, which never develop cerebral aneurysms. Under hemodynamic stress augmented by experimental treatments, further degenerative changes of the internal elastic lamina and involvement of the medial layer are considered to occur and result in aneurysm formation there.

Animals↗

Degradation of phospholipid molecular species during experimental cerebral ischemia in rats.

Previous investigators have shown that free fatty acids that accumulate during ischemia are an indicator of evolution in ischemic brain damage. Our study describes the temporal relations between free fatty acid accumulation and degradation of phospholipid molecular species after cerebral ischemia. Using the four-vessel occlusion model of adult Wistar rats, we analyzed quantitatively the cerebral phospholipid molecular species of diacyl phosphatidylcholine and diacyl phosphatidylethanolamine and released free fatty acids during ischemia. Total diacyl phosphatidylcholine molecular species decreased gradually but did not show any significant difference even at 60 minutes. By contrast, total diacyl phosphatidylethanolamine abruptly decreased after 5 minutes and continued to decrease significantly thereafter. Polyunsaturated molecular species showed a higher ratio of degradation than saturated and monounsaturated molecular species of either phosphatidylcholine or phosphatidylethanolamine. Total free fatty acid accumulated according to the time elapsed, and statistical significance was obtained after 10 minutes. Free arachidonic and docosahexaenoic acids were attributed to these significant accumulations at 10, 15, and 30 minutes. At 60 minutes, individual free fatty acids increased nonspecifically. Free fatty acids, which are hydrolyzed from phospholipid classes, are known to be further metabolized to bioactive substances such as prostaglandins and leukotrienes. Rapid degradation of phospholipid molecular species, especially of diacyl polyunsaturated molecular species, could be an important finding to membrane perturbation. Effective prevention of these changes might enhance tolerance to ischemic brain damage.

Animals↗

Tonsillar herniation on magnetic resonance imaging.

To evaluate the risk of tonsillar herniation, the caudal pole of the cerebellar tonsil in posterior fossa mass lesions and anomalies was investigated with magnetic resonance imaging. The cerebellar tonsil was clearly demonstrated in relation to the surrounding structures on T1-weighted images in the paramedian or midline sagittal plane. In 78% of a control group of 50 cases, the tonsil was located just on or close to the upper border of the posterior lip of the foramen magnum. It was close to the line of the foramen magnum in 4 cases (8%), but displacement below this line was not observed in any case. In 18 cases of posterior fossa mass lesions, the tonsil tended to be in a lower position than in the control group, and tonsillar displacement below the foramen magnum was noted in 3 cases. Two of these cases had anterior medullary displacement with loss of the cerebrospinal fluid (CSF) space anterior to the tonsil; these patients had either rapid clinical deterioration or severe papilledema. In the remaining case and in 3 additional cases of Chiari malformation, the tonsils were displaced into the cervical canal with preservation of the CSF space, and the patients showed no signs of rapid clinical deterioration or increased intracranial pressure. The present study suggests that tonsillar displacement through the foramen magnum with associated anterior medullary displacement and loss of the CSF space anterior to the tonsil can be regarded as a sign of tonsillar herniation.

Adolescent↗

Ruptured aneurysm of the posterior spinal artery of the upper cervical spinal cord: case report.

A case of aneurysm of the posterior spinal artery of the upper cervical spinal cord is presented. The patient had severe intracranial subarachnoid hemorrhage with disturbance of consciousness. Four-vessel angiograms showed neither anomalous arrangement of the arteries nor arteriovenous malformation intracranially or in the spinal subarachnoid space. Operation disclosed a thrombosed aneurysm of the posterior spinal artery, which was radically excised and histologically examined.

Aneurysm↗

Study on polymorphonucleocytal elastase-alpha 1-protease inhibitor complex in bronchoalveolar lavage fluid (BALF).

The purpose of the present study is to determine polymorphonucleocytal elastase-alpha 1-protease inhibitor complex in bronchoalveolar lavage fluid (BALF) in order to investigate the clinical significance of the increased complex in BALF. BALF was collected by the usual method using a bronchial fiberscope and concentrated 5-10 folds by Amicon UM-2 ultrafiltration. Determination of the complex in BALF and plasma was made in accordance with the method of Neumann et al. The level of complex (microgram/mg albumin, mean value) in BALF was 0.38 in healthy non-smokers (n = 5), 3.14 in healthy smokers (n = 6), 5.61 in the patients with chronic obstructive pulmonary disease (COPD) (n = 9) and 1.78 in the patients with idiopathic pulmonary fibrosis (IPF) (n = 15), that is, higher in healthy smokers and COPD and IPF patients. The ratio of the complex in BALF vs plasma was higher in healthy smokers and in COPD patients than in healthy non-smokers. Furthermore, there was a positive correlation between the level of this complex in BALF and the number of PMN in BLAF (r = 0.68, p less than 0.01). From the above it was assumed that the release of elastase from PMN is progressed in the lower airway of smokers and COPD patients.

Adult↗