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Biomedical subjects

K Ohtsuka

Publications and source records attributed to K Ohtsuka.

At least 145 records · Page 8Linked to original sources
PubMed1995

Transcranial magnetic stimulation over the posterior cerebellum during visually guided saccades in man.

Recent intensive neurophysiological experiments in the monkey have demonstrated the function of the cerebellum in the control of saccadic eye movements. Microstimulation studies on monkeys have determined that the cerebellar cortex, which is specifically involved in the control of saccades, is located in vermal lobules VIc and VII. The Purkinje-cell axons arising from this vermal area terminate almost exclusively in an ellipsoidal region which protrudes dorsocaudally from the fastigial nucleus. Saccade-related cells in the fastigial nucleus are located exclusively in the ellipsoidal region. Microstimulation of the vermis modulated the activity of saccade-related cells in the fastigial nucleus, and then produced dysmetric saccades. In this study, we investigated effects of cerebellar stimulation on saccade metrics in man using a transcranial magnetic stimulation (TMS) device. Focal TMS was applied over the posterior cerebellum at an area approximately 7 mm lateral and caudal to the inion during horizontal visually guided saccades in six normal subjects. The TMS device was triggered after the onset of saccades with a latency of 0, 20, 40 or 60 ms. We investigated the effect of TMS on the amplitude and velocity of saccadic eye movements. For visually guided saccades directed contralateral to the stimulation side, TMS of the posterior cerebellum with the latency of 0 ms produced hypometric saccades followed by corrective saccades. Transcranial magnetic stimulation with latencies of 20, 40 and 60 ms had no effect on saccade metrics. On the other hand, for ipsilateral saccades, TMS with latencies of 0, 20 and 40 ms produced hypermetric saccades followed by postsaccadic drift.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Role of heat shock cognate 70 protein in import of ornithine transcarbamylase precursor into mammalian mitochondria.

The roles of the 70-kDa cytosolic heat shock protein (hsp70) in import of precursor proteins into the mitochondria were postulated to be related to (i) unfolding of precursor proteins in the cytosol, (ii) maintenance of the import-competent state, and (iii) unfolding and transport of precursor proteins through contact sites, in cooperation with matrix hsp70. We examined roles of cytosolic hsp70 family members in import of ornithine transcarbamylase precursor (pOTC) into rat liver mitochondria, using an in vitro import system and antibodies against hsp70. Immunoblot analysis using an hsc70 (70-kDa heat shock cognate protein)-specific monoclonal antibody and a polyclonal antibody that reacts with both hsc70 and hsp70 showed that hsc70 is the only or major form of hsp70 family members in the rabbit reticulocyte lysate. The hsc70 antibody did not inhibit pOTC import when added prior to import assay. However, when pOTC was synthesized in the presence of the antibody and then subjected to import assay, pOTC import was markedly decreased. pOTC import was also decreased when the precursor was synthesized in the lysate depleted for hsc70 by treatment with hsc70 antibody-conjugated Sepharose. This reduction was almost completely restored by readdition of purified mouse hsc70 during pOTC synthesis. The readdition of hsc70 after pOTC synthesis and only during the import assay was not effective. Thus, once import competence of pOTC was lost, hsc70 was ineffective for restoration. Newly synthesized pOTC lost import competence in the absence of hsc70 somewhat more rapidly than in its presence. These results indicate that hsc70 is required during pOTC synthesis and not during import into the mitochondria. hsc70 presumably binds to pOTC polypeptide and maintains it in an import-competent form.

Animals↗
PubMed1995

Discharge properties of Purkinje cells in the oculomotor vermis during visually guided saccades in the macaque monkey.

1. We previously described discharge properties of cerebellar output cells in the fastigial nucleus during ipsilateral and contralateral saccades. Fastigial cells exhibited unique responses depending on the direction of saccades and were involved in execution of accurate targeting saccades. Purkinje cells in the oculomotor vermis (lobules VIc and VII) are thought to modulate these discharges of fastigial cells. In this study we reexamine discharge properties of Purkinje cells on the basis of this hypothesis. 2. Initially we physiologically identified the right and left sides of the oculomotor vermis. Saccade-related discharges of 79 Purkinje cells were recorded from both sides of the vermis during visually guided saccades toward the sides ipsilateral and contralateral to the recording side in two trained macaque monkeys. To clarify the correlation of Purkinje cell discharge with burst activities in the fastigial nucleus during saccadic eye movements, we analyzed our data by employing methods used in the study of fastigial neurons. 3. Among the 79 cells, 56 (71%) showed burst discharges during saccades (saccadic burst cells). Of the 56 cells, 29 exhibited a peak of burst discharges in both the contralateral and ipsilateral directions (bidirectional cells). The remaining 27 saccadic burst cells showed a peak of burst discharges during either contralateral or ipsilateral saccades (unidirectional cells). Among the 79 cells, 14 (18%) exhibited a pause of discharges during contralateral saccades (pause cells). Among the 79 cells, 9 (11%) showed burst discharge during contralateral saccades followed by tonic discharge that was correlated with eye position (burst tonic cells). 4. The timing of bursts in bidirectional cells with respect to saccade onset was dependent on the direction of saccade. During ipsilateral saccades, Purkinje cells exhibited a long lead burst that built up gradually, peaked near the onset of the saccade, and terminated sharply near midsaccade. The mean lead time relative to saccade onset was 29.3 +/- 24.5 (SD) ms. During contralateral saccades, Purkinje cells exhibited a short lead/late burst that built up sharply, peaked near midsaccade, and terminated gradually after the end of the saccade. The mean lead time relative to saccade onset was 10.7 +/- 20.8 ms. The burst onset time during contralateral saccades and the burst offset time during ipsilateral saccades preceded the saccade offset time by about the same interval regardless of the saccade amplitude. 5. In pause cells the pause preceded saccade onset by 17.5 +/- 10.6 ms. The duration of the pause was not correlated with the duration of saccades. There was little trial-to-trial variability in the onset time of the pause with respect to the onset of saccades, whereas there was large trial-to-trial variability in the offset time of the pause with respect to the offset of saccades. In addition, the mean onset time of the pause for each cell had a relatively narrow distribution. 6. The burst lead time of burst tonic cells relative to saccade onset was 9.5 +/- 3.9 ms. The tonic discharge rate of burst tonic cells was a nonlinear function of eye position. The regression of each cell was fit to two lines. The regression coefficient ranged from 0.95 to 0.99 (mean = 0.97). 7. Axons of Purkinje cells in the oculomotor vermis are thought to project exclusively to saccadic burst cells in the fastigial oculomotor region (FOR), which is located in the caudal portion of the fastigial nucleus. Our previous studies indicated that FOR cells provide temporal signals for controlling targeting saccades. The present results suggest that Purkinje cells in the oculomotor vermis modify the temporal signals of FOR cells for saccades in different directions and amplitudes. The modification of FOR cell activity by Purkinje cells is thought to be essential for the function of the cerebellum in the control of saccadic eye movements.

Action Potentials↗
PubMed1995

Cotranslocation and colocalization of hsp40 (DnaJ) with hsp70 (DnaK) in mammalian cells.

A novel 40-kDa heat-shock protein hsp 40 in mammalian cells has been recently identified to be a homolog of bacterial DnaJ protein. We have previously shown the colocalization of hsc70 (p73, constitutive form) with hsp40 in the nucleoli of heat-shocked HeLa cells. In this report we further investigated intracellular translocation and localization of hsp40 and hsp70 (both constitutive p73 and inducible p72) in several mammalian cells. Translocation kinetics of hsp40 during heating at mild temperature were almost the same as those of hsp70 in HeLa cells. Hsp40 colocalized not only with hsc70 (p73) but also with hsp70 (p72) in heat-shocked HeLa (human), HA-1 (Chinese hamster) and NRK (rat) cells. Direct interaction of hsp40 with hsp70 (p73 and/or p72) was observed in all cells tested by immunoprecipitation methods. Also, treatments of cells with cytoskeleton-acting drugs such as cytochalasin E, colchicine and taxol had no effect on the heat-induced translocation of hsc70 (p73) and hsp40 in NRK cells. These results strongly suggest that hsp40 and hsp70 (p73/p72) form a complex in the cytoplasm at normal temperature, translocate together and colocalize in the nuclei and nucleoli upon heat-shock, and that they may function cooperatively to repair (refold) denatured proteins under stress conditions.

Animals↗
PubMed1995

Adult T cell leukemia clinically manifested with ascites and pleural effusion.

A 62-year-old man with adult T cell leukemia (ATL) presented with complaints of anorexia and abdominal fullness. Evaluation revealed ascites and pleural effusion, but no lymph node swelling, hepatosplenomegaly, or skin involvement. The diagnosis of ATL was made by the detection of specific surface markers for T lymphocytes in pleural effusion and ascitic fluid, and by determination of human T cell leukemia virus type I (HTLV-I) proviral DNA integration in mononuclear cells of pleural effusion. This case was considered a rare type of ATL with infiltration of the pleura and peritoneum.

Ascites↗
PubMed1995

Adhesion molecules on intermediate TCR cells. I. Unique expression of adhesion molecules, CD44+ L-selectin-, on intermediate TCR cells in the liver and the modulation of their adhesion by hyaluronic acid.

In addition to thymus-derived T cells, it was demonstrated recently that extrathymically differentiated T cells exist in the liver and other immune organs of mice. Since such extrathymic T cells have T-cell receptors (TCR) of intermediate intensity (i.e. intermediate TCR cells) and constitutively express IL-2 receptor beta-chain (IL-2R beta) similar to natural killer (NK) cells, they are easily distinguished from thymus-derived T cells with a TCR-bright+ IL-2R beta- phenotype (i.e. bright TCR cells). In the present study, the expression of adhesion molecules CD44 and L-selectin was compared between these T-cell subsets. Intermediate TCR cells in the liver and other organs were found to be CD44+ L-selectin- and, inversely, bright TCR cells were CD44- L-selectin+. CD3- IL-2R beta+ NK cells were also estimated to be CD44+ L-selectin-. Hyaluronic acid, which is known to adhere to a CD44 ligand, bound to intermediate TCR cells, but not to bright TCR cells. Among many extracellular matrices, hyaluronic acid induced a prominent decrease in the numbers and proportions of intermediate TCR cells and NK cells in the liver from 6 to 24 hr after in vivo administration. The half-life span of injected hyaluronic acid was approximately 7 hr in the plasma. These results suggest that the CD44 molecule, which is uniquely expressed on intermediate TCR cells and NK cells, is eventually associated with their adhesion to the sinusoidal walls in the liver.

Animals↗
PubMed1995

Transcranial magnetic stimulation of the posterior parietal cortex degrades accuracy of memory-guided saccades in humans.

PURPOSE: Previous neurophysiological studies in the monkey have shown that the posterior parietal cortex (PPC) is involved in the control of memory-guided saccades. In this study, the authors investigated the effect of focal transcranial magnetic stimulation (TMS) over the posterior parietal cortex on accuracy of memory-guided saccades in humans to clarify the cortical region related to controlling memory-guided saccades. METHODS: Single TMS pulses were applied systematically at various locations over the parietal cortex during memory-guided saccades in human subjects. Each subject was instructed to fixate on a central target until the target was extinguished. A lateral target was flashed for 100 msec with unpredictable direction and amplitude. The subject executed a saccade to the remembered position of the previously flashed target in total darkness when the central target was extinguished. Transcranial magnetic stimulation was applied after the extinction of the central target with various latencies. Stimulation sites were identified by three-dimensional magnetic resonance imaging (MRI). RESULTS: Transcranial magnetic stimulation of the right PPC degraded accuracy of rightward and leftward memory-guided saccades in all subjects, when TMS was applied 100 msec after the offset of the central target. On the other hand, TMS of the left PPC showed no effects on accuracy of memory-guided saccades. Systematic error of saccade amplitude appeared as a hypometria for rightward saccades. Three-dimensional MRI revealed that the effective stimulation site was located over the posterior portion of the intraparietal sulcus and the superior part of the angular gyrus of the right hemisphere. CONCLUSIONS: These findings strongly suggest that the right PPC is involved in maintaining spatial accuracy of remembered target locations of memory-guided saccades in humans.

Adult↗
PubMed1995

Heat-shock protein 40, a novel predictor of thermotolerance in murine cells.

We have investigated the relationship between the synthesis of hsp-40, recently identified as a mammalian homologue of DnaJ protein, as well as hsp-70 and the development of thermotolerance in cells of the mouse squamous cell carcinoma line SCCVII. Thermotolerance as determined by clonogenic survival was induced not only by prior heating at 44 degrees C for 30 min but also by prior treatment with 100 microM sodium arsenite for 1 h and 5 micrograms/ml prostaglandin J2 for 4 h. These treatments concomitantly induced both hsp-70 (p72, inducible form) and hsp-40. The extent of thermotolerance correlated well with the relative amount of hsp-70 and hsp-40. These results suggest that hsp-40 is a good predictor of thermotolerance in addition to hsp-70.

Animals↗
PubMed1995

[Examination on the courses of the arteries in the axillary region I. The course of the subscapular artery system, especially the relationships between the arteries and the posterior cord of the brachial plexus].

The subscapular artery (Sbs) is the largest and most variable branch of the axillary artery (Ax). Although this Sbs has been defined as a common trunk of the thoracodorsal artery (TD) and the circumflex scapular artery (CS), TD and CS do not always form a common trunk, and the posterior circumflex humeral artery (CHP) is often associated with CS or the CS+TD trunk. Moreover, the subscapular branch (RS) usually arises from CS or CS+TD. Therefore, the subject of the study on Sbs must at least include RS and CHP. However, many anatomical studies on Sbs variation have not included them, and the mechanism causing the variation of Sbs has not been treated except in a few papers. Yamada distinguished two types of subscapular artery in 1967. The first type arose from Ax proximal to the point where Ax passed between the lateral and the medial cord or penetrated the ventral stratum of the brachial plexus. The second type arose from Ax distal to the point. The former type crossed over the medial cord of the plexus to reach the upper lateral thoracic wall, gave off the lateral thoracic artery (TL) and then ran backward on the serratus anterior muscle to reach the deep region of the axilla. Yamada named the former type Sbs "A.subscapularis superficialis" and considered it to be derived from TL. Yamada made an epoch-making report regarding the arteries of the axilla in 1967. He did not, however, refer to the relationship between the arteries to the deep region of the axilla and the posterior cord of the plexus. We called Sbs and the related arteries to the deep region of the axilla "the subscapular artery system" (Sbs system) and examined the courses of the Sbs system in 202 sides of cadavers during the dissecting practices from 1988 to 1992. Our examination revealed that there were three types of Sbs systems, i.e., S-type, I-type, and P-type Sbs systems. The S-type Sbs system was almost the same as Yamada's "A. subscapularis superficialis", branching off from the lateral thoracic artery arising from Ax proximal to the point where Ax penetrated the ventral stratum of the brachial plexus, and ended up in TD or bifurcating into TD and CS. CHP arose from the proximal part of the TD+CS-trunk and ran via the proximal course, or from CS and via the distal course. The S-type CHP ran posterior to the radial nerve (R). The frequency of appearance of the main arteries of the S-type Sbs system decreased sequentially from the medial artery to the lateral one as follows: TD > CS > CHP. Both the I-type and P-type Sbs system arose from Ax distal to the point where Ax penetrated the ventral stratum of the brachial plexus. But the former ran posterior across the medial side of R and the latter ran posterior across the lateral side. The branching point of the I-type Sbs system from Ax was located more proximally than that of P-type. The I-type Sbs system more often gave off CS than TD and CHP. The P-type Sbs system arose from the most distal part of Ax just in front of the lateral axillary hiatus. The sequence of the frequency of appearance was CHP > CS > TD. Both CS and TD of P-type passed behind R. Different types of Sbs systems coexisted. In such cases, the more proximal type gave off more medial arteries and the more distal type gave off more lateral arteries. Exceptions to the rule, for example, coexistence of P-type CS with S-type CHP or I-type TD with S-type CS etc., were never observed. Although different features were distinguished in the stem parts of the three types of Sbs systems, the courses of the peripheral branches of Sbs systems displayed a common pattern on the surface of the subscapular muscle when they were analyzed collectively disregarding the direction of the flow of blood. Therefore, the peripheral part of each Sbs system on the surface of the subscapular muscle was considered to be derived from a common arterial network. In conclusion, the mechanism of the formation of variations in the Sbs system can be understood by the combination

Axillary Artery↗
PubMed1994

Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones.

The folding of polypeptides emerging from ribosomes was analysed in a mammalian translation system using firefly luciferase as a model protein. The growing polypeptide interacts with a specific set of molecular chaperones, including Hsp70, the DnaJ homologue Hsp40 and the chaperonin TRiC. The ordered assembly of these components on the nascent chain forms a high molecular mass complex that allows the cotranslational formation of protein domains and the completion of folding once the chain is released from the ribosome.

Adenosine Triphosphate↗
PubMed1994

Similarities and differences between extrathymic T cells residing in mouse liver and intestine.

Extrathymic T cells in the hepatic sinusoids and intraepithelial lymphocytes (IEL) in the intestine of mice have both similar and different properties. In this study, both types of extrathymic T cells in mice were further characterized. Lymphocytes obtained from systemic immune organs, including the lamina propria and Peyer's patches, were also compared. Extrathymic T cells in both the liver and the intestine contained a large proportion of gamma delta T cells and expressed the alpha alpha homodimer of CD8. They became more prominent in athymic nude mice and in normal mice with aging, while disappearing in scid mice. Extrathymic T cells in the liver, on the other hand, had TCR of intermediate intensity (i.e., intermediate TCR cells) and IL-2 receptor beta-chains (IL-2R beta) of high intensity, similar to NK cells, whereas IEL had TCR of bright intensity and consisted of cells with both low and high levels of IL-2R beta. Thymus-derived T cells did not express IL-2R beta at all, at least at their resting conditions. Intermediate TCR cells included double-negative CD4-8- cells as well as single-positive cells. In contrast, IEL contained both double-positive (DP) CD4+8+ cells and single-positive cells. More precisely, IEL gamma delta T cells were mainly IL-2R beta + and single-positive (mainly CD8+), while IEL alpha beta T cells were mainly IL-2R beta- and contained both DP CD4+8+ cells and single-positive cells. CD4+ cells were more predominant than CD8+ cells in the liver, while CD8+ cells were overwhelmingly predominant in the intestine. These results suggest that both intermediate TCR cells and IEL are generated as primitive T cells in phylogeny, but later develop along independent pathways at their respective sites.

Aging↗
PubMed1994

Lens accommodation evoked by microstimulation of the superior colliculus in the cat.

Accommodative responses to microstimulation of the superior colliculus (SC) of cats were investigated by measuring dioptric changes of the eye with a high-speed infrared optometer. Lens accommodation was elicited by low-current stimuli (< or = 20 microA) of the rostral portion of the SC, which corresponds to the representation of the central visual field. The low-threshold area for evoking lens accommodation was distributed from the superficial to intermediate layers of the SC. The latency of accommodative responses was 198.3 +/- 34.6 msec (mean and SD). The duration of accommodation was highly correlated with the duration of stimulation. These findings suggest that the SC plays an important role in the control of lens accommodation.

Accommodation, Ocular↗
PubMed1994

A similar expression pattern of adhesion molecules between intermediate TCR cells in the liver and intraepithelial lymphocytes in the intestine.

Two major populations of extrathymically differentiated T cells exist in the liver and intestine. Such T cells in the liver have TCR of intermediate intensity (i.e., intermediate TCR cells) and constitutively express IL-2 receptor beta-chain (IL-2R beta), whereas those in the intestine, especially intraepithelial lymphocytes, have TCR of bright intensity, consisting of a mixture of IL-2R beta+ and IL-2R beta-. All mature thymocytes and thymus-derived T cells seen in the peripheral immune organs are TCR-bright+ IL-2R beta- under resting conditions. When the expression pattern of adhesion molecules, including CD44, L-selectin, LFA-1 and ICAM-1, was compared among these T-cell populations, they displayed quite unique patterns of expression. All extrathymic T cells in the liver, intestine, and even other organs were CD44+ L-selectin-LFA-1++ICAM-1+, whereas thymocytes and thymus-derived T cells were CD44-L-selectin+LFA-1+ICAM-1-. This inverted expression of adhesion molecules between extrathymic T cells and thymus-derived T cells might be associated with their unique tissue-localization.

Animals↗
PubMed1994

Saccadic burst neurons in the fastigial nucleus are not involved in compensating for orbital nonlinearities.

1. To test whether the cerebellum is involved in compensating for orbital nonlinearities, we recorded discharges of saccadic burst neurons in the fastigial oculomotor region (FOR) during both centrifugal and centripetal saccades in two trained macaque monkeys. 2. We also investigated the metrics of centrifugal and centripetal saccades with the same amplitude while output signals from the fastigial nucleus were blocked by muscimol, an agonist of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), injected into the FOR. 3. We studied discharges of 32 fastigial neurons that were inhibited by microstimulation of the oculomotor vermis. These neurons exhibited unique burst responses during contralaterally and ipsilaterally directed saccades, as shown in our previous report. The discharge pattern, the peak burst frequency, the burst lead time, and the burst duration were consistent, regardless of initial eye position. 4. The muscimol injection produced hypermetric saccades toward the injection side and hypometric saccades to the opposite side, regardless of whether saccade was centripetally or centrifugally directed. 5. These findings suggest that the FOR is not involved in the compensation of saccade metrics for orbital nonlinearities.

Animals↗
PubMed1994

The induction of interleukin-6 (IL-6) and colony-stimulating factors (CSFs) by FK565 and its thrombopoietic activity following in vivo administration.

The induction of macrophage colony-stimulating factor (M-CSF) in monkey plasma following administration of FK565 was observed within 2 h of injection peaked at 4 h, and remained high after 24 h. Interleukin-6 (IL-6) and M-CSF levels increased in monkeys treated with FK565, even at doses as low as 0.01 mg/kg. Granulocyte CSF (G-CSF) levels increased slightly following a dose of 1 mg/kg, but granulocyte macrophage CSF (GM-CSF) was not detected at any doses of FK565 studied. To examine the thrombopoietic activity of FK565 in vivo, single doses of drug (0.01, 0.1 or 1.0 mg/kg) were administered i.v. to cynomolgus monkeys or normal mice on day 0. The promotes platelet (PLT) count after FK565 injection decreased transiently on days 1 and 2, and then increased in a dose-dependent manner on day 5 and was still high on day 14. The experiment using anti-PLT antibody showed that the increased PLT count was not simply due to a rebound phenomenon after the transient decrease in PLT. The effect of i.v. FK565 was studied in mice myelosuppressed with a single dose of mitomycin C (MMC) (5.6 mg/kg). The fall in PLT count was suppressed on day 7 by 0.1 and 1.0 mg/kg FK565. Although intact cells or tissues are necessary for an increase in PLT following FK565 treatment, FK565 suppressed the impaired hematopoietic function seen after chemotherapy. FK565 is proposed as a drug to restore reduced neutrophil and platelet counts found in AIDS or cancer therapy.

Animals↗
PubMed1994

The superior alveolar nerves: their topographical relationship and distribution to the maxillary sinus in human adults.

The superior alveolar nerves in human adults were investigated macroscopically using whole-mount silver impregnation, paying special attention to their topographical relationship and distribution to the mucous membrane of the maxillary sinus. In addition, the fiber composition of the alveolar nerves was analysed in order to estimate their contribution to teeth innervation. The posterior superior alveolar nerve (PSAN) ran through canaliculi in the lateral wall of the sinus (23 of 37 cases, 62.2%) or under the mucous membrane of the sinus (14 of 37 cases, 37.8%). Moreover, the PSAN gave off many fine twigs to make complex plexus under the mucous membrane of the sinus before joining the superior dental plexus. The plexus of the maxillary sinus was separated from the superior dental plexus by the bony wall of the sinus. After the above gross observations, the perimeter compositions of myelinated fibers of the plexus, PSAN and the anterior alveolar nerve were analysed in the same specimen. The plexus was composed of myelinated fibers of less than 27 microns in circumference perimeter (mean: 14.3 microns) and numerous unmyelinated fibers. The fiber composition suggested that few fibers in the plexus of the maxillary sinus contribute to the formation of the superior dental plexus. The superior dental plexus, innervating the upper teeth, was located in the thick alveolar process of the maxilla, and not on the maxillary sinus wall. The clinical importance of these results was discussed in relation to nerve injury during antrostomy of the maxillary sinus.

Aged↗