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Biomedical subjects

C Seki

Publications and source records attributed to C Seki.

At least 19 recordsLinked to original sources

[Supplementary motor area epilepsy associated with ADHD in an abused history].

A 6-year-old girl with attention-deficit hyperactivity disorder (ADHD) who had been abused by her mother in infancy developed supplementary motor area (SMA) epilepsy. The seizure was characterized by bilateral tonic seizure of the upper and lower extremities, speech arrest, preserved consciousness and a lack of postictal confusion. The duration of the seizure was usually 10-60 seconds. The seizures sometimes clustered. She was diagnosed as having SMA epilepsy based on the characteristic clinical symptoms, interictal EEG, ictal video-EEG and ictal SPECT. Though her seizure was initially improved by anti-epileptic drugs, the symptoms appeared again after discharge. Since her clinical course indicated that her seizure was aggravated by her mental state, treatment included both medication with anti-epileptic drugs and the adjustment of her living environment in cooperation with a child guidance clinic. Thereafter both her epileptic seizure and ADHD symptoms improved. These changes may be related to each other, because both conditions are associated with frontal lobe dysfunction. It was interesting that the adjustment of the environment improved frontal lobe epilepsy, which in turn ameliorated ADHD symptoms.

Attention Deficit Disorder with Hyperactivity↗

IgG subclass switching is associated with the severity of experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein peptide in NOD mice.

We have recently shown that a single dose of the myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 produces a relapsing-remitting demyelinating disease similar to multiple sclerosis (MS) in Lewis rats. In this study we have assessed the possibility that a subclass of anti-MOG35-55 antibodies influences the clinical outcome of these diseases by examining the classes and isotypes of anti-MOG35-55 antibody produced during the course of MOG35-55-induced demyelinating disease in NOD mice. Following immunization, 7 of the 21 injected mice had only mild diseases, while the 14 others had severe progressive and/or relapsing-remitting diseases. There were no differences in anti-MOG35-55 IgG, IgA, IgM, IgG1, IgG2a, and IgG3 antibody titers between the severe and mild symptoms groups. High levels of IgG2b antibody to MOG35-55 were detected in all mice with severe symptoms. In contrast, none of the mice which contracted a mild disease produced anti-MOG35-55 IgG2b. These results suggest that in NOD mice, the IgG2b antibody response to MOG35-55 is associated with the severity of this MS-like demyelinating disease.

Amino Acid Sequence↗

Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds.

An endogenous cannabimimetic molecule, 2-arachidonoylglycerol, induces a rapid, transient increase in intracellular free Ca2+ concentrations in NG108-15 cells through a cannabinoid CB1 receptor-dependent mechanism. We examined the activities of 24 relevant compounds (2-arachidonoylglycerol, its structural analogues, and several synthetic cannabinoids). We found that 2-arachidonoylglycerol is the most potent compound examined so far: its activity was detectable from as low as 0.3 nM, and the maximal response induced by 2-arachidonoylglycerol exceeded the responses induced by others. Activities of HU-210 and CP55940, potent cannabinoid receptor agonists, were also detectable from as low as 0.3 nM, whereas the maximal responses induced by these compounds were low compared with 2-arachidonoylglycerol. Anandamide was also found to act as a partial agonist in this assay system. We confirmed that free arachidonic acid failed to elicit a response. Furthermore, we found that a metabolically stable ether-linked analogue of 2-arachidonoylglycerol possesses appreciable agonistic activity, although its activity was apparently lower than that of 2-arachidonoylglycerol. We also confirmed that pretreating cells with various cannabinoid receptor agonists nullified the response induced by 2-arachidonoylglycerol, whereas pretreating cells with other neurotransmitters or neuromodulators did not affect the response. These results strongly suggested that the cannabinoid CB1 receptor is originally a 2-arachidonoylglycerol receptor, and 2-arachidonoylglycerol is the intrinsic physiological ligand for the cannabinoid CB1 receptor.

Animals↗

Effect of tracer metabolism on PET measurement of [11C]pyrilamine binding to histamine H1 receptors.

The present study was carried out to investigate the time course of [11C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [11C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [11C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [11C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [11C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [11C]pyrilamine. Based on the rat data, the contribution of 11C-labeled metabolites to total [11C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [11C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [11C]pyrilamine by brain tissue itself. Therefore, [11C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [11C]pyrilamine binding to histamine H1 receptors.

Adult↗

Hemodynamics evoked by microelectrical direct stimulation in rat somatosensory cortex.

The aim of this study was to estimate the timing (latency) of the increase in red blood cell (RBC) velocity and RBC concentration, and the magnitude of response in local cerebral blood flow (LCBF) for neuronal activation. We measured LCBF change during activation of the somatosensory cortex by direct microelectrical stimulation. Electrical stimuli of 5, 10 and 50 Hz of 1 ms pulse with 10-15 microA, were given for 5 s. LCBF, RBC velocity and RBC concentration were monitored by laser-Doppler flowmetry (LDF) in alpha-chloralose anesthetized rats (n = 7). LCBF, RBC velocity and RBC concentration increased nearly proportionally to stimulus frequency, i.e. neuronal activity. LCBF rose approximately 0.5 s after the onset of stimulation, and there was no significant time lag of the latencies among LCBF, RBC velocity and RBC concentration at the same stimulus frequency. We interpret these results to mean that the onset of LCBF increase on cortical activation is reflected by a rapid change in arteriole (resistance vessel) dilation and capillary volume. The data also elucidate the linear relationship between LCBF increase and cortical activity.

Animals↗

CBF change evoked by somatosensory activation measured by laser-Doppler flowmetry: independent evaluation of RBC velocity and RBC concentration.

The purpose of this study was to examine the timing and magnitude of cerebral blood flow (CBF) responses to neuronal activation. We measured the changes in local CBF (LCBF), red blood cell (RBC) velocity and RBC concentration by laser-Doppler flowmetry (LDF) as well as field potential recordings during activation of the somatosensory cortex of the rat in response to electrical stimulation of the hind paw. Electrical stimuli, 0.1 ms pulses of 1-1.5 mA for 5 s, were applied at 0.2, 0.5, 5, 10 and 50 Hz under alpha-chloralose anesthesia. LCBF showed the maximum increase at 5 Hz, and rose approximately 0.5 s after the onset of stimulation regardless of the frequency. The maximum frequency of the field potentials was also obtained at 5 Hz. During activation of the somatosensory cortex, the onset of rise in RBC concentration did not precede that of RBC velocity, and the peak RBC concentration was noted earlier than that of both LCBF and RBC velocity, suggesting that both arteriolar diameter and active changes in the capillary contributed to the LCBF response.

Animals↗

Application of a beta microprobe for quantification of regional cerebral blood flow with (15)O-water and PET in rhesus monkeys.

A beta microprobe was successfully applied to monitor arterial input function for quantification of regional cerebral blood flow (rCBF) in the monkey brain with (15)O-water and positron emission tomography (PET). The sensitivity of the probe was approximately 0.83 to 1.67 cps/kBq/ml depending on the studies. A preliminary study was performed to find a suitable use and to evaluate the performance of the system and data analysis procedure. The results showed that dispersion correction of measured input function was unnecessary if microprobes were connected directly to the arterial catheter. Then multiple CBF measurements were done in three monkeys under anesthesia. Identical regions of interest were placed with the aid of magnetic resonance imaging (MRI) of each monkey and rCBF values were estimated. Estimated rCBFs were reproducible for several measurements. The mean CBF value for a pentobarbital anesthetized monkey was 46.0 ml/min/100 g (PaCO2 = 46.3 mmHg). This shows that the use of the beta microprobe for quantification of rCBF with PET was validated. The lack of a need for dispersion correction of observed input function is an advantage with the beta microprobe system because the probes are small enough to be placed near the arterial sampling site.

Animals↗

[MRI, SPECT and MRS findings in a case of acute hemiplegia syndrome with a marked hemispheric brain edema].

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS) were successively recorded in a 3-year-old girl with the acute hemiplegia syndrome. She was admitted to our hospital with complaints of fever, loss of consciousness and right side dominant clonic convulsions evolving into status epilepticus, and then recovered with sequelae of aphasia and right hemiparesis. Electroencephalography showed a generalized slow rhythm at the onset, and very low activities on the left hemisphere in the follow-up records. Brain CT and MRI revealed edema of the left hemisphere initially, followed by left side dominant brain atrophy. No cerebral vascular lesion was detected by magnetic resonance angiography. N-Isopropyl-[123I]-iodoamphetamine SPECT showed marked hypoperfusion of the left hemisphere accompanied by crossed cerebellar diaschisis. MRS at the initial stage detected decreased N-acetyl-aspartic acid and increased lactic acid signals in the bilateral hemisphere, which subsequently normalized only on the right side. These findings suggested brain damage and neural cell death in the left cerebral hemisphere, caused by acute encephalopathy. SPECT and MRS are useful new techniques to study the pathophysiology of the acute hemiplegia syndrome.

Acute Disease↗

[The effect of cerebral perfusion pressure on cerebral blood flow in the rhesus monkey during sevoflurane anesthesia].

The effect of cerebral perfusion pressure on cerebral blood flow (CBF) was studied under the normocapnic condition in the rhesus monkey under sevoflurane anesthesia. CBF was measured by means of positron emission tomography technique. After the measurement of CBF at 0.5% sevoflurane as control, the measurement was repeated at 2.0% sevoflurane (1 MAC), when blood pressure was kept at a half of the control value. The measurement was also repeated at the same sevoflurane concentration, when the mean blood pressure was restored with the infusion of angiotensin II. Average CBF as well as regional CBFs were compared between two different mean blood pressures at 2.0% sevoflurane. Average CBF increased significantly (+35%), when the mean arterial pressure was increased by the angiotensin II infusion. All the regional CBFs except at frontal cortex increased significantly (+ about 30%) in response to the increase in the mean arterial pressure. The increase in occipital CBF was greatest (+52%). We conclude that CBF during sevoflurane anesthesia up to 2.0% might become dependent on the cerebral perfusion pressure, indicating the compromised autoregulation of CBF in the rhesus monkey.

Anesthesia, Inhalation↗

[The effect of sevoflurane on regional cerebral metabolism and cerebral blood flow in rhesus monkeys].

The effects of sevoflurane on cerebral metabolism and hemodynamics were studied in rhesus monkeys. Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMR O2) as well as their regional changes were measured by means of positron emission tomography technique. After the measurement of regional CBFs and CMR O2s at 1.5% sevoflurane as control, the measurement was repeated at 3.0% sevoflurane and at the same sevoflurane concentration with the infusion of angiotensin II to restore mean arterial pressure. Regional CBFs and CMR O2s were compared among three different conditions. At 3.0% sevoflurane, regional CBFs increased significantly in response to the increase in the mean arterial pressure, suggesting the inhibition of autoregulation of CBF. However, regional CBF/CMR O2 ratio was not significantly different among the cerebral regions with each condition. It could be concluded that CBF during sevoflurane anesthesia up to 3.0% might become dependent on the cerebral perfusion pressure and the changes in regional CBFs varied among the regions. On the other hand, the ratio of oxygen consumption and delivery was well maintained throughout the brain regions.

Anesthesia, Inhalation↗

[Development of a high resolution beta camera].

We have developed and tested a high resolution beta camera. The beta camera consists of thin CaF2(Eu) scintillator, tapered fiber optics plate, position sensitive photomultiplier tube (PSPMT). The output of the PSPMT is fed to position calculation circuit and accumulated in the memory. The data in the memory is fed to personal computer for display and analysis. We have developed two types of beta cameras. One is 20 mm diameter field of view (FOV) camera, and the other is 10 mm diameter camera. Intrinsic spatial resolutions were 0.8 mm FWHM and 0.5 mm FWHM for 20 mm and 10 mm FOV camera, respectively. We confirmed that developed beta cameras may overcome the limitation of the resolution of the PET camera.

Animals↗

Assessment of foot and mouth disease vaccine potency by liquid-phase blocking ELISA: a proposal for an alternative to the challenge procedure in Argentina.

The lowest expected protection (LEP) at a 95% confidence of 245 foot and mouth disease (FMD) commercial vaccines was calculated from the titres of liquid-phase blocking sandwich ELISA (lpELISA) of cattle sera obtained from 3920 animals at 60 days post-vaccination (d.p.v.) and challenged with live virus at 90 d.p.v. It was found that LEP evaluation is highly specific (i.e. it is able to predict the failure in 100% of the cases) although its ability to predict the challenge (PG test) approval (i.e. sensitivity) comprised only 65% of the vaccines that passed the trial. It was possible, nevertheless, to improve the sensitivity of the evaluation by using an alternative coefficient (Ro), exclusively dependent on the number of animals exhibiting the highest and lowest lpELISA titres in a particular vaccine trial. This coefficient was capable of predicting the PG approval of 90% of the vaccines, yet maintaining acceptable levels of safety (87% of specificity). Based on these results and as a first step towards the replacement of the challenge protocol in Argentina, we propose a swift approval for commercialization of FMD vaccines which are able to reach the highly restricting LEP passmark of 82%, and the rejection of those not reaching the 50% LEP limit. More extensive experience with this new protocol will allow a finer adjustment of the LEP and Ro values and to set more precisely the cut-off points for direct approval or disapproval of vaccines by lpELISA, eliminating the use of live FMDV in the field.

Animals↗

Myocardial perfusion with [11C]methyl triphenyl phosphonium: measurements of the extraction fraction and myocardial uptake.

The present study describes extraction fraction and uptake measurements of the [11C]methyl triphenyl phosphonium (11C-MTP), a promising positron emission tomography (PET) agent for cardiac imaging. PET imaging was performed in mongrel dogs. Under physiological flow conditions 11C-MTP uptake reached a maximum within the first 10 minutes after injection and remained constant during the entire observation period of 80 minutes. Over the same time period, the heart/blood ratio was 46-106:1, and the heart/lung ratio 14:1. Following permanent occlusion of the left anterior descending coronary artery, 11C-MTP uptake in the normally perfused myocardium also reached a maximum at 10 minutes after injection, whereas in the infarcted area there was no significant accumulation of 11C-MTP. For a time period of 80 minutes the noninfarcted/infarcted myocardium ratio was 12:1. Extraction was measured in anesthetized dogs with a double isotope method using 99mTc-HSA as the reference tracer. The extraction fraction was 91% at a flow of 69 mL/min/100g. As flow increased to five-fold (342 mL/min/100g) following administration of adenosine, extraction fell to 61%. Following coronary artery occlusion, the 11C-MTP content in the myocardium was highly correlated (r = 0.93, p < 0.01; y = 10.46 + 0.92x) with the microsphere determined regional myocardial blood flow.

Animals↗

Noncompartmental and compartmental modeling of the kinetics of carbon-11 labeled pyrilamine in the human brain.

The kinetic pattern of a 11C-labeled histamine H1 receptor antagonist, [11C]pyrilamine, was investigated in the human brain by factor analysis of dynamic PET studies. Tissue time activity curves were also processed by compartment model curve fitting preceded by deconvolution analysis. Factor analysis revealed two statistically significant and physiologically meaningful kinetic patterns: one for specific and another for nonspecific binding of the radioligand. From these two factors a compartment model containing two tissue compartments (one for specific binding and another for nonspecific binding and free ligand) was constructed. The two-compartment model was also supported by the impulse response function, which was obtained by deconvolution and showed two components. The factor image constructed from factor two demonstrated a distribution pattern characteristic for brain regions rich (frontal, parietal, and temporal lobes) or poor (occipital lobe and cerebellum) in H1 receptors. Blockade of H1 receptors with unlabeled pyrilamine, diphenhydramine, or hydroxyzine caused a significant reduction of this factor. Blockade produced no significant changes in factor one representing nonspecific binding. We conclude that the kinetics of [11C]pyrilamine in the brain can be described by two tissue compartments, one related to the distribution of the H1 receptors. Factor analysis of dynamic studies can be used to locally separate these two compartments, for identification of regions rich and poor in H1 receptors and for noninvasive quantitative investigation of the effects of H1 receptor blockers such as pyrilamine, diphenhydramine, or hydroxyzine.

Adult↗

Large-scale use of liquid-phase blocking sandwich ELISA for the evaluation of protective immunity against aphthovirus in cattle vaccinated with oil-adjuvanted vaccines in Argentina.

Specific serum activity levels against four reference strains of foot-and-mouth disease virus (FMDV) were evaluated from 1634 animals vaccinated with commercial quadrivalent oil vaccines and from 746 unvaccinated, naive animals, using the liquid-phase blocking sandwich ELISA (lpELISA) test. Cows from the FMDV-free area of Argentina were tested for the absence of specific FMDV antibodies (sp FMDV Abs) and those showing lpELISA titres < 1.0 were grouped in lots of 16 animals. They were vaccinated and challenged at 90 days postvaccination (DPV) with one of four virus strains used for vaccine production and control (prototype strains). Serum samples from vaccinated and control cattle were collected 60 and 90 DPV and the level of sp FMDV Abs was determined by lpELISA. Animals were examined for clinical signs of disease. Results show that serum lpELISA titre levels directly correlate with the percentage of protected animals. It was seen that 100, 98, 93 and 87% of the vaccinated cattle with antibody titre levels > or = 2.1 were protected against challenge with serotypes C85, A87,01 Cas and A79, respectively. Evidence is also presented of seroconversion in a sample of 3-5-month-old calves vaccinated in the field, showing lpELISA titres compatible with protection against the four vaccine viruses as long as 150 DPV. Results reported in this paper strongly support the use of the lpELISA test for a rapid and reliable evaluation of the efficacy of FMDV commercial vaccines as well as for the assessment of the immunological status of cattle in FMDV-free and enzootic regions of South America.

Adjuvants, Immunologic↗

[Survey of histopathological diagnostic services in the Department of Oral Pathology, School of Dentistry, Higashi-Nippon-Gakuen University, 1979-1989].

This study is based on an analysis of oral biopsy specimens that were diagnosed histopathologically in the Department of Oral Pathology, School of Dentistry, HIGASHI-NIPPON-GAKUEN UNIVERSITY from 1979-1989. 1. The total number of specimens during the ten years were 503 (dental hospital: 363, other personal dental clinics: 140), it corresponding to 440 cases (patients). 2. There were 224 men, 210 women, and 6 unknown. 3. The most common cases were radicular cysts 11.1% (49 cases), the second dental granuloma 9.5% (42 cases), followed by fibroma (fibrous polyp) 7.7% (34 cases). 4. The largest group of all specimens were cysts (35.7%), the second inflammatory lesions (28.0%), followed by tumors (26.6%). 5. About 80% of oral tumors were benign and about 20% were malignant. Of 24 cases with malignant tumors, the majority were squamous cell carcinoma (20 cases, 87%), followed by malignant melanoma (2 cases, 8.7%), verrucous carcinoma (1 case, 4.3%), and clear cell carcinoma (1 case, 4.3%). 6. About 13% of all oral tumors were odontogenic tumors, and the most common were ameloblastoma (8 cases, 53.3%), followed by odontoma (5 cases, 33.3%), and cementifying fibroma (2 cases, 13.3%). 7. The most common cases of specimens from other dental clinics were radicular cysts (23 cases, 16.4%), the second fibroma (fibrous polyp) (17 cases, 12.1%), and followed by dental granuloma (15 cases, 10.1%).

Female↗

Phospholipase A2 from Bothrops alternatus (víbora de la cruz) venom. Purification and some characteristic properties.

One single protein species with phospholipase activity has been isolated from Bothrops alternatus venom by a procedure involving gel-filtration on Sephadex G-50 (Step 1), chromatography on SP-Sephadex C-50 (Step 2) and gel-filtration on Sephadex G-75 (Step 3). The purified sample behaved as a homogeneous, monodisperse protein with a molecular weight of 15,000 and isoelectric point of 5.04. The yield in enzyme activity was 48% of the starting material and the apparent purification was 51-fold. When assayed on 1,2-diheptanoyl- or 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine, fatty acids and lysolecithins were the only reaction products, in accordance with the predicted stoichiometry. Studies on positional specificity suggested that the enzyme is a phospholipase A2. The enzyme requires Ca2+ ions for activity and exhibited stereochemical specificity, since the enantiomeric 2, 3-diheptanoyl-sn-glycero-1-phosphorylcholine was not hydrolyzed. Under the experimental conditions employed, reaction products representative of either phospholipase B or C activities could not be detected. After Step 1, the phospholipase activity recovered was higher than the total activity in the crude venom sample, which is explained by the separation of an inhibitor during enzyme purification. The inhibitor was responsible for the initial lag period that characterized the kinetics of the enzyme reaction with crude venom acting on aggregated substrates (lipoprotein, vesicles or micelles), while the rate of hydrolysis of monomeric lecithins was not affected.

Animals↗