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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 865 records · Page 48Linked to original sources

Transposition rates of movable genetic elements in Drosophila melanogaster.

A considerable proportion of visible mutations is reported to be caused by the insertion of mobile genetic elements in Drosophila and other organisms. We estimated transposition rates of some Drosophila mobile elements by using the lines AW and JH in which spontaneous mutations have been accumulated independently for about 400 generations. Occupied sites of the mobile elements were detected by in situ hybridization on the salivary gland chromosomes sampled from 40 AW and 30 JH lines. The rates of insertion and excision of the copia and two copia-like elements, 412 and 17.6, are very low: Insertions occurred at up to 10(-3) per second chromosome per generation (17.6) and excision occurred at about 10(-5) per site per generation (copia and 412). Insertions of the I and hobo elements occurred much more frequently. These estimates are not only important for assessing the actual rate of various types of mutations but also for developing an evolutionary theory of mobile elements themselves.

Animals↗

Mapping of brainstem lesions by the combined use of tests of visually-induced eye movements.

To determine the diagnostic value of visually-induced eye movements for indicating the lateralization of the lesion, optokinetic nystagmus (OKN), fixation-suppression of caloric nystagmus and pursuit eye movements were investigated in 28 patients who showed discrete unilateral brainstem lesions. In all patients, pursuit gains decreased in parallel with the direction of the impairment of slow-phase OKN velocity with a significant left/right difference. Decreases of gains were predominantly towards the affected side in 22 patients, whereas they were predominantly towards the contralateral side in 2 patients with dorsal tegmental pontine lesions and in 4 out of 8 patients with Wallenberg's syndrome. The relationship of pursuit gains to percentage reduction of fixation-suppression of caloric nystagmus (%FS) showed no correlation. The following four groups were classified. In group A, which was the largest, pursuit gains and %FS decreased predominantly towards the lesioned side. This group consisted of 5 patients with lesions in the midbrain, 6 patients with lesions in the ventral pons and 4 out of 8 patients with Wallenberg's syndrome. The opposite of group A was group D, showing reverse electro-oculographic (EOG) patterns to those in group A in relation to the lesioned side. Group D consisted of 2 patients with lesions in the dorsal pontine tegmentum. This observation, taken together with the decreases of pursuit and OKN gains in relation to the lesioned side, might indicate that lesions of ascending fibres are responsible for pursuit and OKN abnormalities. Group B, consisting of 7 patients with lesions either in the superior or middle cerebellar peduncles, showed decreased pursuit gains predominantly towards the lesioned side and %FS reduced predominantly towards the side contralateral to the lesion. EOGs of these patients were consistent with the results of floccular ablation in the monkey. In group C, these two parameters showed patterns opposite to those in group B in relation to the lesioned side and this group consisted of the other 4 patients with Wallenberg's syndrome. In patients of this group, the inferior cerebellar peduncle might be involved. The combined use of these tests is thus useful for lateralizing the lesion in the brainstem.

Brain Diseases↗

Increased variation in ADH enzyme activity in Drosophila mutation-accumulation experiment is not due to transposable elements at the Adh structural gene.

We present here a molecular analysis of the region surrounding the structural gene encoding alcohol dehydrogenase (Adh) in 47 lines of Drosophila melanogaster that have each accumulated mutations for 300 generations. While these lines show a significant increase in variation of alcohol dehydrogenase enzyme activity compared to control lines, we found no restriction map variation in a 13-kb region including the complete Adh structural gene and roughly 5 kb of both 5' and 3' sequences. Thus, the rapid accumulation of ADH activity variation after 28,200 allele generations does not appear to have been due to the mobilization of transposable elements into or out of the Adh structural gene region.

Alcohol Dehydrogenase↗

Is the site of action of ketamine anesthesia the N-methyl-D-aspartate receptor?

Synaptic mechanisms underlying ketamine anesthesia were studied using in vitro preparations of the lamprey CNS. Although lampreys are one of the most primitive vertebrates, the synaptic physiology and pharmacology are similar to those in the higher vertebrates. Axonal conduction, transmitter release from the presynaptic terminal, postsynaptic response to the putative neurotransmitters, and resting and activated membrane properties were studied in the absence and the presence of various concentrations of ketamine. Ketamine markedly reduced N-methyl-D-aspartate (NMDA)-activated responses, such as depolarizations to bath-applied NMDA and bursting rhythm during "fictive locomotion." The 50% block of the responses took place in the presence of 10-20 microM ketamine, whereas those induced by kainate and quisqualate (the other two subclasses of L-glutamate/L-aspartate agonists) were spared at concentrations higher than 600-800 microM. None of the other neuronal events tested were suppressed in the presence of still higher concentrations of ketamine. The results support the hypothesis that ketamine might exert its anesthetic effect by a pharmacologically specific interaction with the NMDA receptor.

Action Potentials↗

Selective effect of KB-2796, a new calcium entry blocker, on cerebral circulation: a comparative study of the effects of calcium entry blockers on cerebral and peripheral arterial blood flows.

The effects of a new calcium entry blocker, KB-2796, on cerebral and peripheral circulation were compared with those of four other calcium entry blockers (flunarizine, cinnarizine, nicardipine, and diltiazem) and also papaverine in anesthetized dogs. KB-2796 increased the vertebral blood flow to the same extent as the other drugs. KB-2796 and the other drugs increased the coronary blood flow, although the effect of KB-2796 was obviously weaker than that of the other drugs. The dose of KB-2796 producing a 30% increase in coronary blood flow was about 20 times higher than that producing an equivalent increase in vertebral blood flow. KB-2796 and the other calcium entry blockers caused a moderate increase in both femoral and common carotid blood flow. The renal artery showed a biphasic response to all drugs, which consisted of an initial decrease and a subsequent increase in the flow. From these results, it is suggested that KB-2796 is a new type of calcium entry blocker that selectively affects the cerebral circulation. It is also concluded that calcium entry blockers have a different spectrum of vasodilatory action on coronary and cerebral vascular beds and that a selective coronary vasodilatory action is not a common feature among all calcium entry blockers.

Animals↗

Chondrocyte-like colony formation of mesenchymal cells by dentin extracts in agarose gel culture.

In this study, the effects of guanidine extracts from demineralized bovine dentin matrix on rat mesenchymal cells were investigated by use of an agarose gel culture. The dentin extracts were divided into water-soluble and -insoluble fractions. Rat mesenchymal cells obtained from the cultivation of skeletal muscle tissue and embedded in agarose gel were treated with these two fractions. After three weeks of cultivation, the treated cells formed colonies that were stained metachromatically with toluidine blue in a dose-dependent manner. The activity necessary to form chondrocyte-like colonies by the water-insoluble fraction was significantly higher than that by the water-soluble fraction. Each chromatographic fraction of the water-insoluble part of dentin extracts on tandem Sephacryl S-200 High-resolution columns was also investigated. Chondrocyte-like colony-forming activity was concentrated in a single fraction. However, the electrophoretic pattern of this fraction revealed that there were still some bands of molecular weight between 18 and 30 kDa. According to the Western blot analysis of this fraction, there was a band corresponding to purified transforming growth factor beta (TGF-beta) under the non-reducing condition. After reduction, this band disappeared and we found a band corresponding to a component of 13 kDa as well as TGF-beta. These findings suggest that TGF-beta is present not only in bone but also in the dentin matrix.

Animals↗

Physiochemical properties of phenobarbital solid dispersion with phosphatidylcholine.

We prepared a phenobarbital (PB) solid dispersion (SD) with phosphatidylcholine (PC). PB was present in an amorphous state in SD if its mole fraction was under 0.75. An infrared (IR) spectra study suggested a hydrogen bond between NH in PB and phosphate in PC, with a ratio of about 1:1. When the mole fraction of PB was less than 0.50, differential scanning calorimetry (DSC) curves showed endothermic peaks at 57, 90 and 145 degrees C, and an exothermic peak at 60 degrees C. The IR spectrum and X-ray diffraction pattern changed after holding at 70 degrees C, so at this point it is considered that the metastable state of SD changed into a stable state, and extra energy was released. When the mole fraction of PB was high, PB also arranged near hydrophobic group because an endothermic peak was observed at 46-52 degrees C, which was lower than fully hydrated PC. PB is similar to indomethacin (IM) in molecular shape and to phenytoin (PHT) in chemical structure. Its DSC curve and IR spectra are similar to PHT, and the limit ratio of its amorphous state is the same as IM. It is considered that the chemical structure is an important factor in its interaction to PC, and also, the molecular shape is important to arrange into PC lattice.

Calorimetry, Differential Scanning↗

The release of hepatic triglyceride lipase from rat monolayered hepatocytes in primary culture.

The release of hepatic triglyceride lipase from cultured rat hepatocytes and its hormonal regulation were studied. The activity of lipase released into the medium in the presence of heparin was increasing for 24 hours on the 2nd day of culture. The activity in the absence of heparin was only 10% of that in the presence of heparin. When hepatocytes were cultured with anti-hepatic triglyceride lipase IgG, the lipase activity was suppressed by 92%. The results suggest that the enzyme released into the culture medium is identical to hepatic triglyceride lipase which can be released only in the presence of heparin, the mode of release being similar to that of lipoprotein lipase from adipocytes. The addition of colchicine and monensin to the medium resulted in the inhibition of lipase secretion by 20% and 61%, respectively. Insulin enhanced lipase activity only 20%, whereas dexamethasone suppressed the activity by 44%. These data indicated that hepatic triglyceride lipase is secreted and released from hepatocytes in the presence of heparin and its secretion is regulated by hormones.

Animals↗

[Effects of lead on drug metabolizing enzymes, cytochrome P-450 and hemeoxygenase in rats].

The effects of lead on the drug metabolizing system in liver microsomes and porphyrin metabolism in the bone marrow were studied using male Wistar rats (about 250 g in weight). To study the acute effects of lead, rats were given lead injection intraperitoneally once a day for three consecutive days at a dose of 0 (control), 0.1, 1.0, 10 or 50 mg/kg of lead in the form of lead acetate in a 5% glucose solution. In the 2nd experiment, the chronic effects of lead were studied by administering lead at a dose of 0 (control), 5 and 20 mg/kg once a week for 9 wk for a total of 10 administrations. After the last injection, each rat was fasted for 22 h in a metabolic cage to prevent the animal from eating bed chips or feces and was then sacrificed by decapitation. The rat liver microsome enzymes were used to evaluate the effects of lead on the hepatic functions. In the acute stage, lead decreased the activities of drug metabolizing enzymes, such as aniline hydroxylase and aminopyrine N-demethylase, and decreased the contents of microsomal cytochrome P-450 and cytochrome b5. In the chronic stage, lead decreased the cytochrome P-450 and cytochrome b5 contents and induced hypertrophic liver, but did not affect the activity of aniline hydroxylase. These findings suggest that the rat gradually gained resistance against lead toxicity in the chronic stage. In a supplementary experiment, lead was found to decrease the contents of heme in the microsome and to increase the activity of hemeoxygenase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regenerating nodules in hepatic cirrhosis: MR findings with pathologic correlation.

To establish clearly the pathologic basis for small low-intensity nodules seen on MR images of the cirrhotic liver, we obtained MR images in 26 patients with cirrhosis in whom partial hepatectomy for hepatoma (15 patients), laparoscopy for cirrhosis (10 patients), or autopsy (one patient) was subsequently performed. Small low-intensity nodules were seen on gradient-echo images with short TEs (10-13 msec) in 13 of the 26 patients. In 12 of these 13 patients, small low-intensity nodules appeared larger and clearer as the TE was prolonged (14-25 msec). On T2-weighted spin-echo images, small low-intensity nodules were seen in 12 of the 13 patients, but not seen as well as on gradient-echo images. Pathologic correlation in these 13 patients revealed that the nodules on the MR images corresponded to iron deposits in regenerating nodules. Small low-intensity nodules were observed only on T2-weighted spin-echo images in two of the remaining 13 patients, in whom microscopic examination of the liver revealed marked inflammatory cell infiltration in the fibrous septa and no iron deposition. We conclude that small low-intensity nodules observed on MR images are caused by iron deposits in regenerating nodules, and that gradient-echo images with short and prolonged TEs are useful to confirm the presence of iron deposits in regenerating nodules.

Adult↗

Clinical studies on the occurrence and the pathogenesis of optociliary veins.

We reviewed retrospectively 20 cases of optociliary vein over the past 5 years. Fifteen of the 20 cases (75%) were over 40 years of age. There was no sex differences (9 males and 11 females). Causative ocular diseases were: central retinal vein occlusion (14 cases, 70%); optic disc drusen (2 cases, 10%); and optic nerve sheath meningioma, high myopia, glaucoma, congenital anomaly (1 case each, total 20%). The number of patients with an optociliary vein was high in central retinal vein occlusion (14/190 cases, 7.4%). We concluded that occurrence of optociliary vein is not restricted to cases with optic nerve sheath meningioma and this shunt vessel may occur under other conditions in which central retinal venous return is seriously disturbed. The most common cause of optociliary vein is central retinal vein occlusion.

Adolescent↗

[Clinical feature of odontogenic maxillary sinusitis--symptomatology and the grade in development of the maxillary sinus in cases of dental maxillary sinusitis].

Odontogenic maxillary sinusitis may occur by draining of an apical dental root abscess into the maxillary sinus. It has been reported that the disease is usually frequent in cases aged of the second and third decades. In most of them, either the first or second molar tooth is assumed to be the origin of the disease. As clinical characteristic symptoms, it is mentioned that an acute unilateral sinusitis appears since the onset and the patient complains a fetid purulent nasal discharge from an early stage. The symptom and its clinical time course in 43 cases with dental maxillary sinusitis, who had been treated by surgical procedures in ENT Clinic in Kitasato University Hospital during past 14 years from 1972 to 1985, were studied retrospectively. The size of the affected maxillary sinus in each case of the disease was measured from the X-ray films. An influence of development of the maxillary sinus to the occurrence of dental sinusitis was discussed by comparing the sizes of the maxillary sinuses in both the group of the disease and the group of simple unilateral maxillary sinusitis.

Adolescent↗

[Acute hearing loss in the contralateral ear after acoustic tumor removal].

Two patients suffered from acute hearing loss of the contralateral side after acoustic tumor surgery were reported. The first patient was a 42-year-old-male. He had had a right progressive hearing loss over two years and CT scan revealed a mass of 20mm in diameter in the right cerebellopontine angle. The patient noticed the contralateral hearing loss on next morning after the total removal of tumor by translabyrinthine approach. However he had no complaint of vertigo or facial palsy. An audiogram of the contralateral side just after the onset showed flat type audiogram of sensorineural hearing loss with positive recruitment. With steroid therapy for two weeks, hearing and ABR findings improved and returned to nearly normal. The second case was a 47-year-old male. The patient had chronic renal failure treated by hemodialysis. His hearing loss in the right ear had gradually decreased over two years and an acoustic tumor of 2.5cm in diameter was demonstrated by CT scan. The tumor was removed by translabyrinthine approach. Nine day after the operation, he noted total deafness in contralateral ear and vertigo. He was given steroid hormone and his hearing improved up to 68 dB. Four cases have been reported in the literature. The mechanisms of acute sensorineural hearing loss observed in these cases were discussed. The cause remained unknown, however there were some hypothesis such as the compression to the opposite brainstem, peripheral nerve or feeding vessels by tumor or brain edema after operation, and local vasospasms might be also the cause of hearing impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist.

(S)-(+)-6-(2-Chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl - 2,3,4,5 - tetrahydro - 8H - pyrido[4',3':4,5] thieno[3,2-fl-[1,2,4]triazolo]4,3-a][1,4]diazepine (E-6123) is a newly synthesized platelet-activating factor (PAF) antagonist. The effects of E-6123 on in vitro and in vivo PAF-induced responses were investigated. The IC50 values of E-6123 on 3H-PAF binding to human and guinea pig platelets were 2.7 and 3.0 nmol/l, respectively, and those on PAF-induced platelet aggregation in platelet-rich plasma of human, guinea pig and beagle dog were 10.1, 14.7 and 16 nmol/l, respectively. Oral administration of E-6123 at 3 and 10 micrograms/kg to dogs inhibited ex vivo PAF-induced platelet aggregation in a dose-dependent manner. In guinea pigs, E-6123 at 3 micrograms/kg completely inhibited ex vivo PAF-induced platelet aggregation up to 8 h and the inhibition was still significant at 24 h after administration. Occupancy of the platelet PAF receptor by E-6123 at 3 h and 24 h after administration amounted to 80% and 56%, respectively. Bronchoconstriction induced by PAF injection in guinea pigs was inhibited dose-dependently by oral or intravenous administration of E-6123 at similar doses. The IC50 value of E-6123 at 3 h after oral administration was 1 microgram/kg. Oral administration of E-6123 at 3 micrograms/kg inhibited the bronchoconstriction by more than 90% up to 8 h. Hemato-concentration induced by PAF injection in guinea pigs was inhibited by oral administration of E-6123 at 10 micrograms/kg. E-6123 also protected mice from PAF injection-induced death in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Ischemic cerebrovascular complication in tuberculous meningitis; a case of Fröhlich syndrome and hemiparesis].

A 34-year-old man came to our hospital with an episode of focal convulsion of the left arm. He had suffered from tuberculous meningitis in childhood and developed left hemiparesis and Fröhlich syndrome as sequelae. CT scan showed a calcified mass in the suprasellar cistern and a low density area suggestive of cerebral infarction in the right anterior cerebral artery distribution. The left carotid angiograms showed severe stenosis of the left internal carotid artery in the supra-clinoid segment and occlusion of the proximal middle and anterior cerebral arteries with development of moyamoya vessels as collateral circulation. The right carotid angiograms showed similar findings with less collateral circulation. At surgery, the anterior part of the Willis ring was found embedded in the suprasellar calcified granuloma. Recognition of cerebrovascular complication in tuberculous meningitis is important and an early modification of the therapy may improve the outcome.

Adult↗

Performance evaluation of X-ray computed tomography "TCT-700S".

The performance of the CT scanner "TCT-700S" (Toshiba Medical), including noise, spatial and contrast resolution, and exposure, was evaluated. Noise increased as the slice thickness decreased. No matter what the slice thickness, noise was great when the product of tube current and scan speed (described by mAs in the following sentences) was small. Furthermore, the short scan speed caused considerable large noise. Reduction of the mAs value caused remarkable increase in noise when the slice thickness was 1 mm or 2 mm. At combinations of slice thicknesses of 1 mm or 2 mm and 100 mAs, noise was 1-1.5%. When slice thicknesses were measured as the spatial resolution, in the case of a slice thickness of 1 mm, the measurements were 1.6 to 1.8 mm. When high and low contrast resolutions were measured, maximum diameters for the recognition were large as slice thickness became thinner. Although average exposure promised the improvement in the contrast resolution, great exposure increases failed to contribute to such improvement. These performances depended on the exposure. In the case of multiple scanning, average exposures in the field were uniform. However, at a minimum scan speed of 1.8 sec, a three fold discrepancy occurred in exposures observed reciprocally from the left and right sides. Average exposures were also almost the same with slice thicknesses of 10 mm, 5 mm and 2 mm, but with a slice thickness of 1 mm, average exposure was twice as great. This measurement indicates inadequate collimation in the case of a slice thickness of 1 mm. These average exposures were proportional to the mAs value. The radial-exposure profile depended on the position in the columnar object. Although similar average exposures were observed, high peak values were observed on the upper side, but exposure tended to spread at the bottom in the center. This means that the primary x-ray amounts were great in the peripheral region and scattered x-ray amounts were great at the center.

Evaluation Studies as Topic↗