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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 847 records · Page 47Linked to original sources

Acetylcholinesterase-containing neurons in the striatum, septum and hippocampus of the rat in embryonic culture and adult in situ.

Neurons of the rat brain, of either adult in situ or embryonic culture, have been studied by using a sensitive method for acetylcholinesterase (AChE) histochemistry. In the culture system, incubated for 6-18 days, AChE-positive neurons were found in tissues originating from the striatum and septum, but not in those from the hippocampus. These positive somata were morphometrically analyzed in terms of the cell size, i.e. the lengths of the major axis (Lmax) and the minor axis (Lmin) in cultured dishes of the striatum and septum; the mean Lmax was 20 and 22 microns, respectively. In in situ adult brain sections, a similar morphometric examination of AChE-positive neurons gave comparable results to those obtained in the culture system. An evaluation of both in vitro and in vivo through the histogramatical analysis revealed that the striatum contained more than two populations of AChE-positive cells differing in cell size. In contrast, a major single peak of Lmax was detected in the histogram of the septum. In both cases of striatum and septum in in situ adult brain, sagittal sections show larger size of Lmax, indicating that AChE-positive neurons are arranged in the sagittal direction. In studies on electrophysiological properties of large striatal cells in culture, both acetylcholine and glutamate induced changes in the membrane potential and/or the frequency of excitatory postsynaptic potential, while dopamine induced much smaller responses.

Acetylcholinesterase↗

[Myelography for nerve root avulsion in birth palsy].

Myelography and CT myelography (CTM) were reviewed in 18 cases of birth palsy with clinically suspected avulsion injury. Root-somatosensory evoked potential (root-SEP) was also reviewed for myelographic evaluation of the nerve root avulsion in birth palsy. Root-SEP is not induced in case of avulsed nerve roots, but is induced in case of both normal and incompletely avulsed roots. Myelography demonstrated 58 abnormal nerve roots in 18 cases (19 limbs); 45 (78%) complete and 13 (22%) incomplete nerve root avulsions. Each of complete and incomplete avulsions was defined as total absence and partial presence of rootlets on myelography, respectively. Traumatic meningoceles were detected at 46 roots (79%) on myelography and/or CTM; 35 roots on myelography and 45 roots on CTM. CTM could not detect only a very small meningocele at one root. At 11 roots CTM was superior to myelography in delineating a meningocele because CTM is sensitive to a poorly enhanced meningocele. CTM, however, could not diagnose nerve root avulsions so accurately as myelography, since myelography detected 12 (7 completely and 5 incompletely) avulsed roots without meningocele, whereas CTM could not delineate the nerve roots clearly. Thus, myelography is indispensable to evaluate nerve root avulsions without meningocele. Root-SEP was examined in 9 patients who underwent brachial plexus exploration. SEP was negative at 22/25 roots with complete avulsion and was positive at 7/7 roots with myelographically incomplete avulsion, regardless of presence or absence of any traumatic meningocele.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

The dose-response relationship for N-methyl-D-aspartate currents in cultured rat septal neurons: effects of magnesium ions and 2-amino-5-phosphonovaleric acid.

Dose-response relations of the peak ionic current induced by N-methyl-D-aspartate (NMDA) under Mg-free vs normal saline (1.2 mM Mg) conditions were obtained in cultured neurons dissociated from septa of fetal rat brains using the single electrode voltage clamp method. The effect of D,L-2-amino-5-phosphonovalerate (APV) on the dose-response relationship was also studied. In the Mg-free condition, the response to NMDA increased progressively with dose up to 0.2 mM, at which point the response saturated up to 1 mM NMDA (ED50 was about 70 microM). At larger doses (1-3 mM) the response increased sharply. In normal saline the response increased up to doses of 10 mM, and there was no apparent plateau. In a comparison between the depressant effects of APV and Mg ions on the peak current value, the depression caused by APV (10-30 microM) at higher NMDA concentrations was larger than that caused by Mg.

2-Amino-5-phosphonovalerate↗

Effects of pertussis toxin on inhibition of synaptosomal tyrosine hydroxylase activity by apomorphine.

The effects of pertussis toxin (PTX) on synaptosomal tyrosine hydroxylase (TH) activity and on the inhibition of synaptosomal TH activity by apomorphine were investigated. Exposure of striatal synaptosomes to PTX does not affect basal- or forskolin-stimulated TH activity, but attenuates apomorphine-elicited inhibition of forskolin-stimulated synaptosomal TH activity. There is a good correlation between the attenuation of apomorphine-elicited inhibition of synaptosomal TH activity by PTX and (-)-sulpiride, suggesting that G proteins are involved in the dopamine (DA) autoreceptor-mediated regulation of the enzyme activity. The exposure of synaptosome to PTX results in a 40-50% inactivation of Gi and Go proteins, which is evident from the reduction of ADP ribosylation with [32P]NAD of the remaining G proteins following preincubation with the toxin. The present study also demonstrates that striatal synaptosomal preparations can be used for investigations of the molecular properties of nerve terminal DA autoreceptors.

Adenosine Diphosphate↗

[Diffusion imaging using three orthogonal diffusion encoding gradients].

A new pulse sequence for in vivo diffusion measurements by magnetic resonance imaging is introduced. The proposed sequence employed gradient sensitization in three orthogonal directions to accentuate the effects of diffusion. The amplitudes and durations of the diffusion encoding gradients were carefully selected to achieve optimal signal-to-noise ratio in diffusion imaging. The pulse sequence was implemented on a superconducting whole body imager operating at 1.5 T. The self-diffusion coefficient of water in a bottle was measured to be 2.17 +/- 0.089 X 10(-9) m2/sec at 23 degrees C consistent with other previous measurements. A preclinical study with a human volunteer was also performed and results were presented.

Brain↗

Effects of velocity profile of to-and-fro pulsatile flow on magnetic resonance signal intensity.

The effects of to-and-fro pulsatile flow, i.e., an oscillatory fluid motion with no net flow, on signal intensity in gated spin-echo magnetic resonance imaging are considered both theoretically and experimentally. On the basis of hydrodynamic principles, to-and-fro pulsatile flow at large Womersley numbers consists of uniform inner flow and boundary-layer-type flow adjacent to a tube wall. Therefore, the velocity profile is "trapezoidal" rather than parabolic at all times during the pulsation period. Contrary to the absence of phase dispersion and loss of signal within the inner flow where no velocity gradient exists, large velocity differences cause phase dispersion and, hence, loss of signal within the boundary layer, whose thickness is inversely proportional to the Womersley number. An understanding of these features of to-and-fro pulsatile flow provides the theoretical basis of cerebrospinal fluid flow phenomena in magnetic resonance imaging, since this type of flow exists in cerebrospinal fluid pathways.

Cerebrospinal Fluid↗

Effects of a novel PAF antagonist, E6123, on PAF-induced biological responses.

E6123 is a new member of the benzodiazepine class of PAF antagonists. Although it has similar activity in vitro to the two representative antagonists WEB2347 and Y24180, in vivo it is far more active than these compounds. Thus E6123 was effective in inhibiting dose-dependently PAF-induced bronchoconstriction when administered orally or intravenously (IC50 1.0 and 1.3 micrograms/Kg, respectively, at 3 hr), and had a minimum effective dose of 10 micrograms/Kg and 3 micrograms/Kg, respectively, against PAF-induced hematoconcentration and edema at 3 hr after oral administration. Furthermore, E6123 protects mice from PAF-induced death dose-dependently (ED50 7 micrograms/Kg at 3 hr). In conclusion, E6123 should prove valuable in pharmacological and clinical research into the roles of PAF, and in therapy of diseases such as asthma, in which PAF is assumed to play a pathological role.

Animals↗

Effects of a novel PAF antagonist, E6123, on passive anaphylaxis.

E6123 inhibited antigen-induced bronchoconstriction, the development of bronchial hyperreactivity and eosinophil infiltration in the airway in passively sensitized guinea pigs and protected mice from anaphylactic death. The inhibitory effects of E6123 on anaphylactic response were very potent compared with those of WEB 2347 and Y-24180.

Anaphylaxis↗

The rare inversion with a P element at the breakpoint maintained in a natural population of Drosophila melanogaster.

We found a rare inversion which is superimposed on the In(2R) NS chromosome. It has been maintained for several years in the Raleigh, N.C., USA population and possibly for more than ten years in the southern populations of the USA. Both the breakpoint of the rare inversion and the corresponding site of the In(2R) NS chromosome have P elements and therefore, the rare inversion might be induced by P element activity in a natural population.

Animals↗

Intracranial haemodynamics in diffuse and focal brain injuries. Evaluation with transcranial Doppler (TCD) ultrasound.

Intracranial haemodynamics were studied in 20 patients with diffuse and focal brain injury and experimental animals with acute intracranial hypertension by the use of TCD ultrasound. The mean flow velocity in the middle cerebral artery (MCA) commonly decreased on the side of the haematoma depending on intracranial pressure (ICP) elevation and cerebral perfusion pressure (CPP) reduction in focal injury. The decrease of the MCA flow velocity returned to normal after treatment. The flow velocities decreased bilaterally and there was no difference between the right and left side in diffuse injury. But the velocities increased in spite of ICP elevation when diffuse cerebral swelling developed. Cerebrovascular CO2 reactivity was impaired in two groups of patients with low Glasgow Coma Scale (GCS) scores. The mean velocity of the MCA and blood flow in the internal carotid artery exhibited flow patterns which changed correlatively depending on CPP reduction in experimental animals. Noninvasive study by use of TCD ultrasound can provide valuable information on variant haemodynamic phenomena in patients with diffuse and focal brain injury.

Adolescent↗

Inhibition of protein phosphatases by microcystins and nodularin associated with hepatotoxicity.

Microcystins and nodularin, isolated from toxic blue-green algae, are hepatotoxic monocyclic polypeptides. Both microcystins and nodularin inhibited in vitro protein phosphatase activity present in a cytosolic fraction of mouse liver, bound to the okadaic acid receptors, protein phosphatases 1 and 2A, and thus resulted in the increase of phosphoproteins; this was referred to as the apparent "activation" of protein kinases. Their concentrations causing 50% of the maximal effects are comparable to that of okadaic acid, a potent protein phosphatase inhibitor and a potent tumor promoter, in the nanomolar range of concentration. The increase of phosphoproteins was observed in rat primary cultured hepatocytes and was subsequently associated with morphological changes, which appeared to be a step in the process of hepatotoxicity. The well-known hepatotoxic compounds, alpha-amanitin and phalloidin, did not show any effects similar to those of microcystins, nodularin and okadaic acid. It is suggested that the hepatotoxicity of microcystins and nodularin may result from inhibition of protein phosphatases and the increase of phosphoproteins.

Animals↗

Template-directed oligomerization of 5'-deoxy-5'-nucleosideacetic acid derivatives.

5'-Deoxy-5'-nucleosideacetic acids II-V are isostructural analogues of nucleotides with a carboxylate group in the place of the 5'-phosphate group. We have studied their oligomerization in aqueous solution using a water-soluble carbodiimide as the condensing agent in the presence or absence of an appropriate polynucleotide template. Condensation of adenylic acid analogues IIa, IIIa, and Va in the presence of polyuridylic acid were found to be the most efficient reactions. Cyclization of the activated monomers to lactones and the insolubility of the oligomers in aqueous solution were found to be obstacles to the efficient formation of long oligomers.

Adenosine Monophosphate↗

Isolation and characterization of the minor components associated with microcystins LR and RR in the cyanobacterium (blue-green algae).

Two structurally similar analogues of microcystins LR and RR, cyclic peptide hepatotoxins from Microcystis, were isolated by chromatographic methods. Although they have the same mol. wt and amino acid compositions as those of the parent toxins, they do not possess similar toxicities. Ultraviolet and 1H-NMR spectral data for both components demonstrate clear structural difference of these cyclic peptides from the parent toxins, which are probably responsible for the marked decreases in their observed toxicities.

Amino Acids↗

Testicular metastasis from malignant schwannoma of chest wall.

Metastatic malignancy to the testes is unusual. Reports of testicular metastasis of neurogenic tumor are extremely rare. Only 28 cases with testicular metastasis of neurogenic tumor have been reported in the world literature. Cases of primary malignant schwannoma with testicular metastasis have not been reported previously. We present an unusual case of a thirty-seven-year-old man who had a malignant schwannoma of the chest wall with testicular metastasis.

Adult↗

Synthesis and anti-HIV-1 activity of 2'-"up"-fluoro analogues of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC).

1-(3-Azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (1, FMAU) and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) in the hope that introduction of a 2-"up"-fluoro substituent might potentiate the anti-HIV activity of AZT and DDC. FMAU (1) was converted in three steps into 2,3'-anhydro-1-(2-fluoro-2-deoxy-5-O-trityl-beta-D-lyxofuranosyl)thymine (4), which when treated with NaN3 followed by detritylation afforded 6. F-DDC was prepared by two methods. Tritylation of FIAC followed by treatment of the product with thiocarbonyldimidazole afforded the 5'-O-trityl-3'-O-(imidazolyl)thiocarbonyl nucleoside 9. Upon radical reduction of 9 with Bu3SnH and AIBN, 5'-O-trityl-DDC 10 was obtained. Compound 10 was detritylated to give 12, which (when obtained by this procedure) resisted crystallization, but the diacetate 12' was obtained in crystalline form. Alternatively, FAC (14) was converted into N4,O5'-dibenzoyl derivative 15, which was treated with thiocarbonyldiimidazole. Reduction of 16 with Bu3SnH/AIBN followed by debenzoylation afforded 12, which was obtained in crystalline form. F-AZT did not exhibit any significant activity against the human immunodeficiency virus (HIV) in vitro. F-DDC, however, showed activity against HIV-1, but the therapeutic index is much inferior to that of AZT.

Antiviral Agents↗

Role of Lugol dye endoscopy in the diagnosis of early esophageal cancer.

To evaluate the role of Lugol dye endoscopy in diagnosing early esophageal cancer, we reviewed findings of dye endoscopy and those of conventional endoscopy in 17 early esophageal cancers that were demonstrated as unstained areas on dyeing with Lugol solution. Histologically, all 17 lesions were squamous cell carcinomas; 10 lesions being mucosal carcinomas, the remaining 7 lesions mucosal carcinomas spreading beyond the epithelial layer. The lesions ranged from 0.7 to 4.0 cm in size. Abnormal findings were noted under conventional endoscopy in all but 3 lesions diagnosed only by postoperative pathohistology, regardless of the size and depth of the invasion. Under conventional endoscopy, the following types of morphological changes were noted in 8 (57.1%) of the 14 lesions: slight elevation (1 lesion), depression (6 lesions), and deformed arc (1 lesion). A color change was noted endoscopically in 12 of the 14 lesions (85.7%), this change being redness in all 12 lesions. The unstained area on the resected specimen was consistent with the size of the lesion that was determined by using serially sectioned blocks in all cases. Moreover, the former completely (100%) coincided with the histological area where PAS reaction was weak. In conclusion, under conventional endoscopy, a color change such as redness is an important indicator of minute or superficial esophageal cancer, as is such morphological change as depression, elevation or deformed arc. On the other hand, Lugol dye endoscopy is very helpful in detecting esophageal cancer unassociated with any morphological or color change. It also provides accurate information about the extent of the cancer.

Aged↗