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Biomedical subjects

M Kurachi

Publications and source records attributed to M Kurachi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Direct visualization and characterization of stable microtubules from the neurites of cultured dorsal root ganglion cells.

We tested the stability of microtubules (MTs) in the neurites of cultured dorsal root ganglion cells by dissolving the cytoplasmic membrane with detergent and exposing them to defined extracellular medium under observation with a video-enhanced differential interference contrast (DIC) microscope. Smooth cytoplasmic filaments visualized after membrane removal were suggested to be MTs by the preservation of all of the filaments in the presence but not in the absence of taxol. They were further confirmed to be MTs by specific immunostaining with anti-tubulin antibody. A significant number of MTs in the established neurites of 6-day-old cultures remained longer than 10 min after membrane removal while MTs in the Schwann cell processes or in the distal regions of the growth cone-bearing neurites of 3-day-old cultures disappeared within 2 min. A population of very stable MTs persisting longer than 30 min was also found specifically in the 6-day-old cultures. Association with other structures or bundling seemed to stabilize the MTs to some degree. The most stable MTs, however, were not associated with some structure along the length but were mainly anchored at points, suggesting that specific point attachments may be another important mechanism operating in MT stabilization. The present method is thus capable of directly demonstrating the unusual stability of neuritic MTs, and provides a new system for further investigation on the mechanism of stabilization.

Animals↗
PubMed1997

Saccadic eye movements and regional cerebral blood flow in schizophrenic patients.

This study examined saccadic eye movements, using simple stationary targets, in schizophrenic patients. The targets were eight black points or eight arabic-numbered points placed in randomized order on the circumference of a circle. Self-paced eye movements during clockwise tracking of these points, by 23 patients and 23 controls, were recorded using an infrared eye-mark recorder. Then the relationship between the saccades and clinical symptoms was investigated. Finally, the relationship between the performance of the saccades and resting regional cerebral blood flow (rCBF) was examined using single photon emission computed tomography with 99mTc-hexamethyl propyleneamine oxime (HMPAO). The results indicate that patients track with significantly fewer correct scores and more deviant scores than controls, in agreement with our previous study. There were two groups of patients: an ordinary group who obtained a full-target-hitting score at a 200-ms setting and a fast group who obtained the full score at 100 ms but not at 200 ms. Some patients displayed significantly more hypermetria than controls. Significant correlations were found between hallucination and delusion symptoms and correct score. With respect to relative rCBF, fast-group patients showed significantly decreased rCBF in the left limbic and inferior parietal areas as compared with ordinary group patients. These findings suggest that some schizophrenic patients view the stationary targets too fast and this may be related to dysfunction in the limbic-parietal association area in the left hemisphere.

Adolescent↗
PubMed1996

Reduced microtubule-nucleation activity of tau after dephosphorylation.

Based on video-enhanced differential interference contrast (DIC) microscopy, we developed a small-scale method which is capable of measuring both the lengths and the number densities of microtubules (MTs) assembled in vitro. With this method, effect of dephosphorylation on the activity of bovine brain tau protein to promote the assembly of tubulin at physiological concentration (15 microM) was quantitatively analyzed. The MT number density was selectively reduced when tau isolated directly in the presence of phosphatase inhibitors (N-tau) was dephosphorylated in vitro (DP-tau), without significant changes in the mean MT length or the binding affinity toward preformed MTs. Tau obtained from brain MTs (MT-tau) also exhibited lower nucleation activity in spite of its high MT-binding affinity. The results indicate that nucleation, elongation and MT-binding are distinct aspects of tau function which are differentially affected by the phosphorylation state of tau.

Animals↗
PubMed1996

The characterization of the effect of locally applied N-methylquipazine, a 5-HT3 receptor agonist, on extracellular dopamine levels in the anterior medial prefrontal cortex in the rat: an in vivo microdialysis study.

In this study, we examined the effect of n-methylquipazine (NMQ), which is a putative 5-hydroxytryptamine3(5-HT3)receptor agonist, on the extracellular concentrations of dopamine (DA) and one of its metabolites, dihydroxyphenylacetic acid (DOPAC), in the anterior medial prefrontal cortex (AmPFc) of awake, freely moving rats. The administration of NMQ via the perfusion fluid produced a concentration-dependent (10-1,000 microM) increase in extracellular DA levels in the AmPFc. In contrast, NMQ produced a decrease in the extracellular concentrations of DOPAC. The increase in extracellular DA levels returned to baseline after the removal of NMQ from the perfusate. The increase in extracellular DA levels in the AmPFc produced by 100 microM of NMQ was markedly attenuated by either the coadministration of tetrodotoxin (1 microM), which inhibits axonal impulse flow, or the depletion of extracellular Ca2+ by removing CaCl2 and adding EDTA to the perfusate. The intradialysate administration of the 5-HT3 antagonist BRL 46470A produced a concentration-dependent (10-1,000 microM) decrease in extracellular DA levels, and this effect was reversible on removal from the perfusate. In contrast, ondansetron (500 and 1,000 microM), which is another 5-HT3 receptor antagonist, produced a transient increase followed by a sustained decrease in extracellular DA levels. The preinfusion of 10 microM of BRL 46470 followed by coperfusion of BRL 46470A with 50 or 100 microM of NMQ via the dialysis probe did not significantly attenuate the increase of NMQ in extracellular DA levels in the AmPFc. The administration of the selective 5-HT2 receptor MDL 100907 (1 mg/kg, i.p.) also did not alter the increase in basal DA levels produced by 100 microM of NMQ. The pretreatment of rats with alpha-methyl-p-tyrosine produced a significant attenuation in the NMQ-induced increase in extracellular DA levels, suggesting that the elevation by NMQ of DA levels is dependent on newly synthesized stores of DA. Overall, these results suggest that the increase in AmPFc DA levels by NMQ is probably not mediated by its interaction with the 5-HT3 receptor.

Animals↗
PubMed1996

Brain SPECT of Creutzfeldt-Jakob disease.

SPECT imaging with I-123 IMP or Tc-99m HMPAO was performed in two patients with Creutzfeldt-Jakob disease to evaluate abnormalities in brain perfusion. In the first patient, there was decreased perfusion of the left frontal, parietal, and temporal lobes. CT and MRI were negative. In the second patient, there was patchy perfusion and slightly decreased perfusion of the right hemisphere. MRI revealed slight brain atrophy and bilateral high intensity areas in the basal ganglia on T2 weighted images. Subsequent SPECT imaging revealed severely decreased perfusion of the entire brain. Subsequent MRI demonstrated severe brain atrophy.

Aged↗
PubMed1995

Buckling of a single microtubule by optical trapping forces: direct measurement of microtubule rigidity.

As major determinants of cell shape and polarity, microtubules are required to have suitable rigidity. However, our knowledge of the mechanical properties of microtubules is far from satisfactory. We report here a new method of measuring the flexural rigidity of a single microtubule by direct buckling using the optical trapping technique. Microtubule buckling was induced by applying a small longitudinal compressing force through an optically trapped microsphere that was firmly attached to the microtubule. Three ways of estimating the flexural rigidity of a continuous slender rod, one from the observed critical load of buckling and two from deflected lengths and angles of bending, yielded values which agreed well when applied to the analysis of buckling microtubules. Unexpectedly, we found that the rigidity was not constant as expected but was dependent on microtubule length. This length dependency explains the discrepancies among reported values of microtubule flexural rigidity measured by different methods. Comparing microtubules of identical lengths, microtubules assembled with brain-derived associated proteins (4 x 10(-23) Nm2 at around 10 microns in length) were four times more rigid than those assembled from purified tubulin and stabilized with taxol (1 x 10(-23) Nm2).

Animals↗
PubMed1995

Clinical symptoms and regional cerebral blood flow in schizophrenia.

This study examined the relationship between clinical symptoms and regional cerebral blood flow (rCBF) in schizophrenic patients using single photon emission computed tomography (SPECT). The subjects were 26 medicated schizophrenic patients diagnosed according to DSM-III-R criteria. Clinical symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS), selected items for the Positive and Negative Syndrome Scale (PANSS), and the scale for Schneider's first rank symptoms. Resting rCBF was measured using N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT, and relative rCBF distribution was evaluated in nine regions of interest in each hemisphere. Factor analysis of symptom ratings indicated four separate syndromes: psychomotor poverty, alienation (hallucination and disturbance of the self), delusion, and disorganization. Stepwise multiple regression analysis showed the psychomotor poverty syndrome to be correlated with decreased rCBF in bilateral superior frontal areas and increased rCBF in the left thalamus and right basal ganglia. The disorganization syndrome was correlated with increased rCBF in bilateral anterior cingulates and decreased rCBF in bilateral middle frontal areas. The alienation syndrome was shown related to increased rCBF in the right inferior frontal area and parietal area. Dysfunction in distinctive neural networks involving various prefrontal areas would thus appear to underlie these syndromes in schizophrenia.

Adult↗
PubMed1995

Impaired saccadic eye movements on stationary targets in patients with schizophrenia spectrum disorder.

This study examined tracking eye movements on predetermined stationary targets in patients with schizophrenia spectrum disorder. The targets were 8 black points or 8 arabic-numbered points placed on the circumference of a circle. Self-paced eye movements during clockwise tracking of these points by 23 patients and 23 normal controls were recorded using an infrared eye-mark recorder. Eye movements were analyzed at two settings: firstly, when "fixation point" was defined as a point at which a gaze was held for at least 200-ms; and secondly, when held for at least 100-ms. The results indicated that at the 200-ms setting schizophrenic patients track with significantly fewer correct scores and more deviant scores than controls under black-point conditions. At the 100-ms setting, however, the correct scores of patients were not significantly different from those of controls, although patients displayed more aberrant paths than controls. The superfluous fixations in the patients improved significantly under numbered-point conditions, but patients still achieved lower correct scores than controls. Four of the 23 patients exhibited centering (aberrant path directed toward the center point), suggesting immature control of eye movements under black-point conditions, but not numbered-point conditions. These results suggest that some schizophrenic patients viewed the targets too quickly, and that they have impaired directed attention, which can be improved by cues, and may have impaired preprogramming of eye movements, which is not improved by external cues.

Adolescent↗
PubMed1995

Asymmetry of the ventricle and age at the onset of schizophrenia.

The relationship between lateral ventricular size or its asymmetry and age at the onset of schizophrenia was investigated in 20 schizophrenic patients diagnosed according to DSM-III-R criteria. The ventricle-brain ratio (VBR) was determined using three transaxial slices of magnetic resonance image (MRI) and asymmetry of the lateral ventricle was evaluated from the laterality index of the lateral ventricular area: (left-right/left+right) x 100. Each age at the onset of the prodromal and active phase according to DSM-III-R criteria was determined for each patient. The results showed that asymmetry of the ventricle, but not VBR, was significantly correlated inversely with age at the onset of both the prodromal phase and active phase. Neither asymmetry nor VBR correlated with the duration of illness, age at MRI scanning, or severity of clinical symptoms. It would thus appear that greater asymmetry of the ventricle is associated with earlier onset of schizophrenia.

Adolescent↗
PubMed1995

Esophageal stricture secondary to candidiasis without underlying disease.

Candidiasis of the esophagus progressing to stricture formation in a 74-year-old male is reported. Esophageal candidiasis develops in the presence of various predisposing conditions such as long-standing administration of antibiotics or corticosteroids, and malignancy. The first endoscopic examination of this patient revealed unusual multiple black plaques in the esophagus. Despite intensive exploration, no predisposing factors were found. The stricture was progressive, despite the administration of adequate antifungal therapy, and its presence necessitated several attempts at dilatation. Case reports of esophageal candidiasis without underlying disease are very rare.

Aged↗
PubMed1995

Hypofrontality does not occur with 6-hydroxydopamine lesions of the medial prefrontal cortex in rat brain.

This study examined the effect of lesions of dopamine (DA) nerve terminals the medial prefrontal cortex on local cerebral glucose utilization (LCGU) and dopamine metabolism in the rat brain. Bilateral 6-hydroxydopamine lesions were stereotaxically placed in the medial prefrontal cortex. Twenty-eight days after the lesion, concentrations of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in eight brain regions with a high-performance liquid chromatographic assay. LCGU was assessed by [14C]2-deoxy-D-glucose autoradiography. The lesion produced a striking reduction in DA (to 6% of the control value), and a moderate reduction in DOPAC and HVA in the medial prefrontal cortex. The ratio of DOPAC to DA in the medial prefrontal cortex was significantly elevated in the 6-OHDA lesioned animals. In contrast to DA depletion, LCGU in the medial prefrontal cortex of the lesioned rats was unaltered when compared with the control. These findings suggest that decreased energy metabolism in the frontal cortex, i.e., hypofrontality, does not occur with decreased DA innervation of that site.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effect of 6-hydroxydopamine lesions of the medial prefrontal cortex of the rat on performance in a reaction time task.

Rats were trained to keep pressing a panel and then release it within a time limit after a light cue. Reaction time was measured from the light cue to the release of the panel. In 'regular' preparatory interval (PI) sessions, the rat had to wait (keep pressing the panel) for a light cue during an interval fixed in a session. In 'irregular' PI sessions, which followed regular PI sessions, intervals until a light cue presentation changed randomly from trial to trial in a session. Rats lesioned by 6-hydroxydopamine infusion into their medial prefrontal cortices showed shorter and more stable reaction times in irregular PI sessions than sham-operated control rats. Cross-over patterns of reaction time of the lesioned rats were not as clear as those of the control rats. Impairment of mnemonic predictive function might underlie the reaction time features in irregular PI sessions in the lesioned rats.

Animals↗
PubMed1995

Effects of 6-hydroxydopamine lesions of the medial prefrontal cortex on local cerebral blood flow and D1 and D2 dopamine receptor binding in rats: a quantitative autoradiographic study.

The effects of lesions of the dopamine (DA) nerve terminals in the medial prefrontal cortex (MPFC) on local cerebral blood flow (LCBF) and DA receptor binding in rats were investigated. 4 micrograms of 6-hydroxydopamine (6-OHDA) was infused stereotaxically into the area of the bilateral MPFC of rats pretreated with desmethylimipramine, and control rats received a vehicle solution. Twenty-four days after the operation LCBFs of 23 brain regions were measured using the quantitative autoradiographic N-isopropyl-p-[125I]iodoamphetamine technique D1 and D2 DA receptor binding in various brain regions was also quantified autoradiographically using [3H]SCH 23390 and [3H]YM 09151-2 as the respective ligands. 6-OHDA lesions of MPFC produced significant increases in LCBF of the nucleus accumbens, the dorsolateral portion of the caudate-putamen and the anterior cingulate cortex. The lesioned animals did not show decreased LCBF in MPFC per se. D1 and D2 DA receptor binding was not affected in any brain region examined. These results suggest that lesions of the DA nerve terminals in MPFC induce an enhancement of functional activity in the terminal regions of the subcortical DA systems, and that hypofunction of the mesocortical dopamine system does not elicit reduced metabolic activity in the prefrontal cortex.

Animals↗
PubMed1995

Intussusception of the cecum with calcified fecaliths.

We treated a patient with a complete invagination of the cecum that contained two large laminated calcified fecaliths. Colonofiberscopy showed a dimpling submucosal tumor that was palpated as a bony hard tumor at laparotomy. This finding suggested that the fecaliths caused intussusception of the cecum and that such an intussusception should be suspected when a bony hard, dimpling submucosal tumor is found in the cecum. To our knowledge, this is the first reported case of a cecal invagination accompanied by calcified fecaliths without an appendical intussusception.

Aged↗
PubMed1994

Comparative study of dopamine metabolism with local cerebral glucose utilization in rat brain following the administration of haloperidol decanoate.

The effects of haloperidol decanoate on dopamine (DA) metabolism in discrete regions of rat brain were investigated and compared with changes in local cerebral glucose utilization (LCGU). The concentration of DA and its metabolite, homovanillic acid, and the alpha-methyl-p-tyrosine (alpha-MT)-induced decline of DA were measured in 6 brain regions by a high-performance liquid chromatographic assay. LCGU in 26 brain regions were examined by [14C]2-deoxy-D-glucose autoradiography. At 24-hr after intramuscular injection of haloperidol decanoate (60 mg eq/kg to haloperidol), the concentration of homovanillic acid in the prefrontal cortex, caudate-putamen, accumbens nucleus, lateral amygdala, and medial thalamus showed significant increase compared with control values. On day 21, the increase in these regions was significantly attenuated with no significant difference from the controls. Furthermore, chronic haloperidol rats showed alpha-MT-induced decline of DA to a similar extent in the control rats. LCGU on day 21 showed significant decrease in the parietal cortex, and a tendency toward decrease in the prefrontal cortex, lateral amygdala and medial thalamus compared with the controls. There was no significant change in LCGU in the caudate-putamen or accumbens nucleus. Chronic haloperidol would thus appear to affect energy metabolism mainly in the cortico-thalamo-limbic circuits, and this may not correspond well to presynaptic DA metabolism.

Animals↗