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Biomedical subjects

K Terada

Publications and source records attributed to K Terada.

At least 55 records · Page 3Linked to original sources

Enantiomer separation of pharmaceuticals by capillary gas chromatography with novel chiral stationary phases.

New chiral stationary phases of polydimethylsiloxane anchored with (S)-(-)-t-leucine derivatives were provided for use in enantiomer separation of pharmaceuticals by capillary gas chromatography. Fifteen pharmaceuticals were separated into their enantiomeric pairs by converting them into pentafluoropropionyl and heptafluorobutyryl derivatives. The separation factor and resolution obtained from the new phases were superior to those from the conventional Chirasil-Val capillary column.

Chromatography, Gas↗

Desynchronization and synchronization of central 20-Hz rhythms associated with voluntary muscle relaxation: a magnetoencephalographic study.

To clarify the cortical mechanisms involved in motor inhibition, modulation of cortical rhythms around 20 Hz during voluntary muscle relaxation was compared to that during muscle contraction in ten normal volunteers, using a whole head type neuromagnetometer. Each subject relaxed or contracted the right forearm muscles, from which electromyograms were recorded. After bandpass filtering magnetoencephalographic signals into frequency bands of 6-10, 10-14, 14-18, 18-22, 22-26, and 26-30 Hz, the signals of each frequency band were rectified and averaged with respect to the onset of motor trial. The relaxation task showed movement-related 20-Hz desynchronization over bilateral central areas beginning a few seconds before the termination of muscle contraction. Twenty-hertz desynchronization was present also for the contraction task at the same location within each subject. The two tasks had a positive correlation among subjects in both the percent decrease (r2=0.76, P<0.01) and the peak time (r2=0.61, P<0.05) for the contralateral 20-Hz desynchronization. After the muscle relaxation, desynchronization was followed by conspicuous movement-related synchronization of the 20-Hz passband in the contralateral central areas, which was significantly larger than that after the contraction (P<0.001). The results suggest that the voluntary muscle relaxation involves the modulation of central rhythms starting a few seconds before the actual event, and the 20-Hz desynchronization has a similar temporal property in the muscle relaxation and contraction. The 20-Hz synchronization in the contralateral central area after the muscle relaxation may be associated with the temporally arrayed termination of the ongoing muscle contraction.

Adult↗

Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes.

BACKGROUND & AIMS: Wilson's disease is a genetic disorder characterized by the accumulation of copper in the body caused by a defect of biliary copper excretion. The Wilson's disease gene has been cloned; however, the precise localization of the gene product (ATP7B) and its role in biliary copper excretion have not been clarified. METHODS: We constructed a chimeric protein between green fluorescent protein (GFP) and ATP7B (GFP-ATP7B) and expressed it in a human hepatoma cell line (Huh7) and isolated rat hepatocytes. The Golgi apparatus, late endosomes, lysosomes, and bile canaliculus were visualized by fluorescence microscopy. Brefeldin A and nocodazole were used to redistribute the Golgi proteins. Bafilomycin A1 was used to analyze the association between GFP-ATP7B and the late endosomes. RESULTS: GFP-ATP7B colocalized with rhodamine-dextran and late endosome markers but not with the Golgi markers, lysosome markers, or a tight junction protein. Brefeldin A and nocodazole redistributed the Golgi proteins, but they did not affect the distribution of ATP7B. CONCLUSIONS: Although it is widely believed that ATP7B is located at the Golgi apparatus, its main localization is in late endosomes. ATP7B seems to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes.

Adaptor Protein Complex gamma Subunits↗

Rationality/antiemotionality personality and selected chronic diseases in a community population in Japan.

OBJECTIVE: To clarify the relationships of the rationality/antiemotionality (R/A) personality with past histories of seven chronic diseases and current smoking habits in a community population in Japan. METHODS: A questionnaire survey was conducted of all residents aged 35 years old or over (n = 37,287) in Takayama city, Gifu prefecture, Japan; the response rate was 90.3%. Data from 13,091 males and 14,061 females who completed all relevant questions were analyzed. The subjects were asked to complete an 11-item R/A personality scale developed by Grossarth-Maticek et al. (1985). Past histories of seven major chronic diseases and current smoking habit were also asked in the questionnaire. RESULTS: Among males, the R/A scale score was significantly lower in those who had stroke, diabetes or allergy than in those who did not. Among females, the R/A scale score was significantly lower in those who had stroke, allergy or stomach cancer than in those who did not. Among females, current smokers had significantly lower R/A scores than non-smokers. After controlling for age, smoking and drinking, the R/A score was significantly and negatively associated with stroke among males and females; it was significantly and negatively associated with diabetes and allergy among males. CONCLUSION: Our findings are contrary to those observed in Yugoslavia and West Germany, and suggest a cultural difference in the relationship between the R/A personality and disease occurrence.

Adult↗

Somatosensory evoked high-frequency oscillations recorded directly from the human cerebral cortex.

OBJECTIVE: To elucidate the generator sources of high-frequency oscillations of somatosensory evoked potentials (SEPs), we recorded somatosensory evoked high-frequency oscillations directly from the human cerebral cortex. SUBJECTS AND METHODS: Seven patients, 6 with intractable partial epilepsy and one with a brain tumor, were studied. With chronically implanted subdural electrodes, we recorded SEPs to median nerve stimulation in all patients, and also recorded SEPs to lip and posterior tibial nerve stimulation in one. High-frequency oscillations were recorded using a restricted bandpass filter (500-2000 Hz). RESULTS: For the median nerve oscillations, all oscillation potentials were maximum at the electrodes closest to the primary hand sensorimotor area. Most oscillations were distributed similar to or more diffusely than P20/N20. Some later oscillations after the peak of P20 or N20 were present in a very restricted cortical area similar to P25. We investigated the phase change of each oscillation potential around the central sulcus. One-third of the oscillations showed phase reversal around the central sulcus, while later oscillations elicited in a restricted cortical area did not. High-frequency oscillations to posterior tibial nerve and lip stimulation were also maximum in the sensorimotor areas. Most of the lip oscillations showed phase reversal around the central sulcus, but most of the posterior tibial nerve oscillations did not. CONCLUSION: High-frequency oscillations are generated near the primary sensorimotor area. There are at least two different generator mechanisms for the median nerve high-frequency oscillations. We suspect that most oscillations are derived from the terminal segments of thalamocortical radiations or from the primary sensorimotor cortex close to the generator of P20/N20, and some later oscillations from the superficial cortex close to the generator of P25.

Brain Neoplasms↗

Quantitative correlation between initial dissolution rate and heat of solution of drug.

PURPOSE: The aim of this study is to estimate the initial dissolution rate of drug substances by isothermal microcalorimetry. A theory was presented on the basis of Gibbs free energy and the Noyes-Whitney equation. METHODS: Polymorphic forms and quenched glass of indomethacin, and some different crystallinity samples of terfenadine were used. The heats of solution of samples were measured by isothermal microcalorimetry. The initial dissolution rates of samples were measured by rotating disk method at 25 degrees C. RESULTS: Each drug showed a linear correlation between the heats of solution and the logarithms of initial dissolution rate, irrespective of their different crystal structure, such as polymorphic forms and crystallinity. The logarithms of initial dissolution rates were well correlated with the degree of crystallinity obtained by the isothermal microcalorimetry. CONCLUSIONS: The initial dissolution rates of drug substances could be estimated quantitatively from the heats of solution as estimated from the present theory. Isothermal microcalorimetry was extremely useful for the estimation of the initial dissolution rates of polymorphs and of partially crystalline samples.

Histamine H1 Antagonists↗

Quantitative relationship between solubility, initial dissolution rate and heat of solution of chiral drugs.

PURPOSE: The aim of this study was to clarify the quantitative relationship between solubility, initial dissolution rate and heat of solution of racemic compound and its enantiomers. METHODS: Propranolol, propranolol HCl, tyrosine, and tryptophan were used as typical chiral drugs. The heat of solution of chiral drug was measured by an isothermal microcalorimeter and the heat of fusion was measured by a DSC. The free energy difference for the dissolution of drug was calculated from the solubility and initial dissolution rate data. RESULTS: The free energy difference and enthalpy difference of the dissolution between the racemic compound and enantiomer of propranolol, propranolol hydrochloride, tyrosine, and tryptophan were obtained by the solubility, initial dissolution rate and heat of solution data. A good linearity was observed in the free energy difference and the enthalpy difference for the dissolution of them, except for propranolol HCl data. By considering the dissociation in solution, the data of propranolol HCl followed the regression line. CONCLUSIONS: The free energy difference of the dissolution was linearly dependent on the enthalpy difference for the racemic compound and its enantiomers. The results fit the theoretical equation. It could be possible to estimate the solubility of chiral insoluble drug from the thermal data.

Hot Temperature↗

Testing for rubella-specific IgG antibody in urine.

BACKGROUND: In Japan rubella vaccination is generally done once during a lifetime, and the vaccination rate decreased after a revised vaccination law in 1995. History of rubella or vaccination may still be unreliable. Testing for rubella antibody is significant to prevent the occurrence of congenital rubella syndrome. However, the collection of blood samples to detect antibodies from young children is invasive and difficult. METHODS: For this study we obtained 853 matched serum and urine samples from 904 healthy students 10 or 14 years of age in the Ibara and Yoshii districts of Okayama, Japan, for a comparison of antibodies for rubella in the matched samples. The serum and urine antibodies were measured with hemagglutination-inhibition and enzyme-linked immunosorbent assays, respectively, and with our urine-based antibody test. RESULTS: The sensitivity, specificity and concordance rates of this urine-based antibody test were 96, 99 and 97% based on the serum antibody results of both assays. The coefficiency was 0.627 between the titers of the urinary and serum antibodies by the enzyme-linked immunosorbent assay. The urinary antibodies were stable for at least 5 months at 4 degrees C and 25 degrees C. CONCLUSIONS: Urine-based assay methods are helpful not only because they avoid the invasive approach of venipuncture but also because unprocessed urine specimens can be used and urinary antibody is stable for a long period. Therefore this test is suitable for screening. In addition protective amounts of rubella antibody in blood can be reliably assessed by means of urine samples.

Adolescent↗

[Comparison of cost and benefits of each model for rubella immunization in Japan].

MMR (measles-mumps-rubella) immunization in Japan was suspended in 1993 due to the high incidence of mumps meningitis as a complication. As a result, immunization coverage for rubella still remains at the 50-60% level in Japan. One way to increase the coverage rate is to increase the frequency of immunization. We calculated the predicted positivity rate of the antibody and cost and the benefits is three models of double vaccination, i.e., vaccination twice. The first model consists of simply two identical vaccinations. The second model consists of two vaccinations with mass vaccination at school for the second immunization. The third model consists of two vaccinations with screening of the urinary antibody for rubella in the second immunization. To calculate the predicted values we used coefficients from Ibara City. The predicted positivity rates and cost increases ranged from 60% to 90% and from 7.3 billion to 12.8 billion yen from the first to third models, respectively. Screening for the urinary antibody should be much cheaper than the presumed price because more than a million subjects will be screened. Since it would cost less than half the price, the third model should be best for the positivity rate of the antibody and cost and benefits. Therefore, we think that third model is the best correction until MMR immunization can be reintroduced.

Antibodies, Viral↗

[Measures against hospital infection for students in medical schools in Japan--a survey by questionnaires].

We sent questionnaires to 80 medical schools in Japan to know what the problems in hospital infection for students in medical schools are. Seventy-one % were sent back to us. There have been hospital infection from patients to students in 12% of the medical schools, included 3 cases each of measles, chickenpox and mumps, 2 cases each of rubella, hepatitis B and tuberculosis. Fourteen % of the medical schools had reports about the past history of infection and vaccination from students, 70% of the schools determined their antibodies and the 28% did nothing. Ninety-three%, 25%, 23%, 18%, and 15%, of the schools determined antibodies for hepatitis B, rubella, measles, chickenpox and mumps, respectively. Some assays of the measurement were low in sensitivity. The cost for the determination was fully paid in 48% of the schools, but only partially supported in 35%. Tuberculin reaction was performed in 40% of the schools and then BCG was done in 57%. Vaccination was recommended in 40% of the schools. The cost of vaccination was all paid in 38% of them, which was only for hepatitis B, and partially supported in 15% of them.

Cross Infection↗

[Comparison of positivity rates for antibodies against measles, rubella, chickenpox and mumps by assays].

Our previous study found mistakes by some doctors in the choice of an assay for determining antibodies in Japan. To compare the positivity rates for antibodies by assays, we measured the antibodies of measles, rubella, chickenpox and mumps from the same sera using such methods as the EIA, HI and CF assays. The subjects were 175 nursing students. The positivity rates for measles, chickenpox and mumps by the EIA assay were 96.6%, 93.7%, and 83.3%, respectively. Those for rubella by the HI and CF assays were 92.0% and 10.1%. The sensitivity rates for measles, chickenpox and mumps by the HI and CF assays, based on the results of the EIA assay, were 75.1%, 102.4% and 69.2% in the HI assay, and 20.6%, 38.7% and 8.0% in the CF assay, respectively. Our previous study showed that the sensitivity of the HI assay for rubella antibody is same as that of the EIA assay in Japan. Currently an EIA assay should be chosen for these antibodies and the HI assay or IAHA assay should be possible selections for rubella and chickenpox. However, international comparison of the cutoff titers for these antibodies should be considered.

Antibodies, Viral↗

Identification and functional analysis of human Tom22 for protein import into mitochondria.

Mitochondria have a receptor complex in the outer membrane which recognizes and translocates mitochondrial proteins synthesized in the cytosol. We report here the identification and functional analysis of human Tom22 (hTom22). hTom22 has an N-terminal negatively charged region exposed to the cytosol, a putative transmembrane region, and a C-terminal intermembrane space region with little negative charge. Tom22 forms a complex with Tom20, and its cytosolic domain functions as an import receptor as in fungi. An import inhibition assay, using pre-ornithine transcarbamylase (pOTC) derivatives and a series of hTom22 deletion mutants, showed that the C-terminal segment of the cytosolic domain is important for presequence binding, whereas the N-terminal domain is important for binding to the mature portion of pOTC. No evidence for pOTC interaction with the Tom22 intermembrane space domain was obtained. Binding studies revealed that the presequence is critical for pOTC binding to Tom20, whereas both the presequence and mature portion are important for binding to Tom22. A cell-free immunoprecipitation assay indicated that an internal segment of the Tom22 cytosolic domain is important for interaction with Tom20.

Amino Acid Sequence↗

Determination of hydration kinetics of sulfaguanidine anhydrate in aqueous solution by calorimetry.

A heat conduction microcalorimeter was used to evaluate the isothermal transition in water from anhydrate to monohydrate at 298 K. Sulfaguanidine (SGN) anhydrate was used as a model compound for the measurement of hydration kinetics in water. It is the well-known that SGN is very slightly soluble in water and capable of existing as the anhydrate or monohydrate form in the solid state. The transition rates of SGN anhydrate to monohydrate in tablets and granules were investigated. The hydration kinetics of tablets with controlled surface areas, obtained by coating the side with paraffin in aqueous solution, followed an apparent zero-order mechanism. On the other hand, the transition mechanism of the granules involved a phase boundary-controlled contracting interface reaction.

Calorimetry↗

Molecular state of chlorpheniramine in resinates.

Chlorpheniramine (CPM) maleate was prepared as a series of resinates by the batch method. The several resinates were investigated by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and infrared (IR) spectrometry. The results from DSC and XRPD showed that the molecular state of the entrapped drug changed from the crystalline to amorphous state. IR spectra indicated that only CPM species was entrapped in the resinates. Moreover, it also showed that the positively charged amine group of the drug interacted with the sulfonate groups of the resin by ionic association. The dissolution of the drug and resinates was also studied where it was found that the dissolution of the resinates was retarded by their crosslinked structure and markedly affected by the quantity of resin.

Calorimetry, Differential Scanning↗

Quantitative detection of apoptotic thymocytes in low-dose X-irradiated mice by an anti-single-stranded DNA antibody.

The quantitative detection of apoptotic cells in low frequency in the thymus of mice irradiated with X-rays using an anti-single-stranded DNA antibody was explored. The antibody against single-stranded DNA (anti-ssDNA) was obtained with rabbits hyperimmunized with complexes of alkaline-denatured calf thymus DNA. AKR female mice were irradiated with 10 to 100 cGy or 4 Gy X-rays; thereafter, thymus sections were prepared at various times after irradiation. The detection and counting of apoptotic cells in the section were performed after histochemical staining using an anti-ssDNA antibody. The results demonstrate that, although sensitive and quantitative detection of apoptotic cells in irradiated thymus using the anti-ssDNA antibody is possible, the sensitivity is lower compared to that of in situ end-labeling methods, such as TUNEL or ISEL. The antibodies could also be used for rat thymus and spleen. In addition, an increase in positively stained cells by both methods was detected as early as 6 min after the irradiation of mice.

Animals↗

Low induction of varicella-zoster virus-specific secretory IgA antibody after vaccination.

Breakthrough after varicella vaccination occurs in approximately 2. 6% approximately 18.6% of immunocompetent children, but the reason has not been demonstrated clearly. As a first defense, specific secretory IgA antibody on the mucosa plays an important role in preventing invasion of microorganisms. To examine induction of varicella-zoster virus (VZV) specific secretory IgA after natural infection and vaccination and its booster mechanisms, 143 salivary samples were tested by ELISA. The VZV-secretory IgA values were significantly higher in the matched children after natural chickenpox than in those after vaccination, although the total secretory IgA did not differ between them. Two (7%) of the vaccinees lacked the sIgA antibody. In the elderly and in immunocompromised children, the VZV-secretory IgA values were no lower than those in healthy children, and they did not lack VZV-secretory IgA. The doctors and nurses taking care of patients with chickenpox had higher values than the other groups as did individuals who had had herpes zoster recently. VZV-secretory IgA was thought to be stimulated by exogenous and reactivated endogenous VZV to neutralize VZV with weak activity. These results suggest that low or no induction of VZV-secretory IgA antibody after vaccination may be one of the possible explanations for a breakthrough.

Aged↗

[Clinical development of antitumor agent in Europe and USA--experience on CPT-11 development].

Irinotecan hydrochloride (CPT-11) was approved first in Japan in January 1994, then in France in May 1995 and in the USA in June 1996. These approvals were given based on Japanese non-clinical data and the clinical data from phase I and II studies conducted independently in each country. It took almost 3 years in Japan to gain approval; however, six months were sufficient for approval in France and the USA. Systems are well established in Europe and the USA for clinical studies and the development of antitumor agents. It appears that, in Europe and the USA, cancer patients are well supported by society and that cancer chemotherapies are well understood in society as well.

Antineoplastic Agents↗

[A case of non-convulsive status epilepticus worsened Wernicke's aphasia reversely].

A 62-year-old right-handed woman had presented progressive speech impediment over 4 months. She was alert without any convulsions or involuntary movements. Neurological examination showed Wernicke's aphasia, constructional apraxia. Her magnetic resonance imaging (MRI) showed an old cerebral infarction in the left parieto-occipital area, in addition to ischemic changes in the bilateral deep white matter. Electroencephalography (EEG) revealed periodic lateralized epileptiform discharges (PLEDs) predominant in the posterior left hemisphere. The PLEDs as well as the cortical symptoms improved after an administration of anti-convulsive agents, thus establishing the diagnosis of non-convulsive status epilepticus (NSE). It should be emphasized that NSE manifesting as Wernicke's aphasia should be distinguished from dementia syndrome because it is a treatable disorder.

Anticonvulsants↗