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M Takada

Publications and source records attributed to M Takada.

At least 343 records · Page 19Linked to original sources

Tyrosine hydroxylase immunoreactivity in cerebellar Purkinje cells of the rat.

Employing tyrosine hydroxylase (TH) immunohistochemistry, we have revealed that TH immunoreactivity occurs in cerebellar Purkinje cells in the rat. These TH-immunoreactive Purkinje cells were distributed predominantly in the crus I & II ansiform lobules and the paraflocculus, and to a lesser extent in the I & X vermal lobules. Since Purkinje cells in such cerebellar regions displayed no immunoreactivity to dopamine-beta-hydroxylase, the TH-immunoreactive Purkinje cells identified in the present study might contain dopamine or L-DOPA.

Animals↗

Ultrastructural localization of calcium in the chick yolk sac membrane endodermal cells as revealed by cytochemistry and X-ray microanalysis.

The yolk sac membrane (YSM) of the chick embryo transports calcium from the yolk into the embryonic circulation during the first half of development, but the intracellular pathway of calcium transport is poorly understood. In the present study, the ultrastructural localization of calcium was investigated in cells of the YSM of 9-day chick embryos. X-ray microanalysis as well as cytochemical techniques performed on yolk sac membrane cells treated with potassium oxalate, potassium ferricyanide and potassium antimonate demonstrated accumulation of calcium in yolk granules, digested yolk products, electron-dense bodies (EDBs; 100-400 nm diameter) and electron-dense granules (EDGs; 30-50 nm diameter). When strontium ions were injected into the yolk, they were incorporated into the endodermal cells and sequestered specifically in EDGs. From these results, we propose that calcium enters the endodermal cells by endocytosis of calcium-containing yolk granules, as well as through calcium channels in the apical cell membrane. In the cytoplasm, digested yolk products, EDBs, and EDGs act as sites of sequestration and accumulation of calcium. Extrusion of intracellular calcium into the extracellular space and embryonic circulation is accomplished by exocytosis of calcium-containing material and via an ion pump in the basal cell membrane.

Animals↗

Collateral projections of trigeminal ganglion neurons to both the principal sensory trigeminal and the spinal trigeminal nuclei in the rat.

Employing a combination of fluorescent retrograde double labelling and immunofluorescence histochemistry for substance P (SP) and calcitonin gene-related peptide (CGRP), we examined collateral projections from single neurons in the trigeminal ganglion (TG) of the rat to both the principal sensory trigeminal nucleus (Vp) and the oral, interpolar or caudal subnuclei of the spinal trigeminal nucleus (Vo, Vi or Vc). In the rats that were unilaterally injected with fast blue (FB) into the Vp and with diamidino yellow (DY) into the Vo, Vi or Vc, neurons labelled with FB and/or DY were observed in the TG ipsilateral to the injections. Of the labelled TG neurons, about 2% were double labelled with both tracers in the rats that were injected with FB into the Vp and with DY into the Vo or Vi, and about 10% were double labelled in the rats that were injected with FB into the Vp and with DY into the Vc. The results indicate that TG neurons sending their axons to the Vp project, by way of axon collaterals, to the Vc more frequently than to the Vo or Vi. Some of the TG neurons double labelled with FB and DY exhibited SP- or CGRP-like immunoreactivity (LI): Of the TG neurons that were double labelled with FB injected into the Vp and with DY injected into the Vo, Vi or Vc, about 38%, 49% and 42%, respectively, displayed SP-LI, and about 54%, 58% and 59%, respectively, showed CGRP-LI.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Laminar organization of the substantia nigra pars reticulata in the macaque monkey, with special reference to the caudato-nigro-tectal link.

A laminar organization of the substantia nigra pars reticulata (SNr) was revealed in the macaque monkey by using an semihorizontal section plane parallel to the long axis of the SNr in the frontal plane. After injecting horseradish peroxidase conjugated to wheat germ agglutinin into the caudate nucleus (Cd) or putamen, anterogradely labelled fibres and axon terminals in the SNr were observed to form parallel bands in the anteromedial-posterolateral direction. After injecting Fast Blue into the superior colliculus, a cluster of retrogradely labelled neuronal cell bodies also formed a single band arranged in the similar anteromedial-posterolateral direction. The cluster was observed along the anterolateral margin of the SNr. This SNr region containing nigrotectal neurons appeared to overlap with one of the bands containing terminals of striatonigral fibres arising from the body of the Cd. The caudato-nigro-tectal link via the anterolateral marginal area might be involved in the control of saccadic eye movements.

Animals↗

Different sensitivity to amiloride of body and tail skins of Rana catesbeiana tadpoles during metamorphosis.

Regional differences in potential difference and short-circuit current between the body (dorsal) and the tail skin during metamorphosis of Rana catesbeiana tadpoles were investigated. In body skin, the potential difference and the short-circuit current across the skin develop in two successive steps. At stage XX, the potential difference and the short-circuit current across the body skins were amiloride-insensitive (1st step). At stage XXII, however, amiloride-sensitive potential difference and the short circuit current appeared (2nd step). By contrast, in tail skin the potential difference and the short-circuit current remained amiloride-insensitive (1st step) even at stage XXIII. Since the tail regresses after stage XXIII, the appearance of the second step could not be followed in vivo. To determine whether or not the second step can be induced in the tail, tail skin was cultured under conditions where the skin survives for a much longer period than it does in normally developing tadpoles. Such cultured tail skin generated the amiloride-sensitive potential difference and the short-circuit current and cultured body skin also generated them. Therefore, development of the 2nd step in the tail skin may be delayed in vivo. To characterize the differences between body and tail skin, skins were mutually grafted between body and tail at stage XIII-XV. The body skin grafted on the tail underwent both the 1st and 2nd steps by stage XXII, whereas the tail skin grafted on the body only showed the 1st step by the same stage. These results suggest that the regional specificity of the skin is already established before the prometamorphic stage.

Amiloride↗

The sites of origin of serotoninergic afferent fibers in the trigeminal motor, facial, and hypoglossal nuclei in the rat.

The sites of origin of serotoninergic afferents in the trigeminal motor (Vm), facial (VII), and hypoglossal nuclei (XII) were studied in the rat by fluorescent retrograde labeling with Fluoro-Gold, in combination with immunofluorescence histochemistry for serotonin (5-HT). The results indicated: (1) The nucleus raphe magnus, nucleus raphe pallidus, and nucleus raphe obscurus contained 5-HT neurons projecting to the Vm, VII or XII. (2) The nucleus raphe dorsalis sends 5-HT fibres to the Vm and VII, but not to the XII. (3) The gigantocellular reticular nucleus pars alpha contained 5-HT neurons projecting to the VII.

Afferent Pathways↗

Deregulated c-fos augments cell proliferation of B cells mediated by lipopolysaccharide.

We have examined effects of the deregulated c-fos protein on the lipopolysaccharide (LPS)-mediated B cell responses using splenic B cells from transgenic lines carrying the mouse c-fos gene under the control of the H-2K (H2-c-fos) and the inducible Mx promoter (Mx-c-fosD). High c-fos expression was induced in Mx-c-fosD B cells by LPS stimulation. DNA synthesis of the B cells from both lines was augmented depending on the amount of exogenous c-fos. This augmentation resulted in the increase of IgM and IgG2b productions in the culture. These results suggest a functional role of c-fos protein in cell cycle progression of the activated B cells.

Animals↗

Direct projections from the midbrain periaqueductal gray and the dorsal raphe nucleus to the trigeminal sensory complex in the rat.

It is well known that analgesia can be produced by stimulation of the midbrain periaqueductal gray and dorsal raphe nucleus. This stimulation-produced analgesia may operate, at least partly, through direct projections to nociceptors in the primary sensory nuclei. In the present study, direct projections from the midbrain periaqueductal gray and dorsal raphe nucleus to the trigeminal sensory complex were studied in the rat. After injection of Phaseolus vulgaris leucoagglutinin into the periaqueductal gray or dorsal raphe nucleus, terminal labeling was found in the principal sensory trigeminal nucleus and the oral, interpolar and caudal subnuclei of the spinal trigeminal nucleus, bilaterally with an ipsilateral predominance. The terminal labeling was prominent in the ventrolateral parts of the trigeminal sensory complex; it was particularly marked in the principal sensory trigeminal nucleus and laminae I and III of the caudal subnucleus of the spinal trigeminal nucleus. After injection of cholera toxin B subunit into the principal sensory trigeminal nucleus or one of the subnuclei of the spinal trigeminal nucleus, retrogradely labeled cells were seen in the periaqueductal gray and dorsal raphe nucleus, bilaterally with an ipsilateral dominance. In the periaqueductal gray they were most often seen in the ventrolateral and dorsolateral subdivisions, but no particular topographic organization was detected in the distribution of retrogradely labeled neurons in the periaqueductal gray and dorsal raphe nucleus after tracer injection into each subdivision of the trigeminal sensory complex. After injections of Fast Blue and Diamidino Yellow, respectively, into the principal sensory trigeminal nucleus and the caudal subnucleus of the spinal trigeminal nucleus on one side of the brain, a number of doubly labeled neurons were found in the periaqueductal gray and dorsal raphe nucleus, bilaterally with an ipsilateral dominance. The results indicate that a considerable number of neurons in the periaqueductal gray and dorsal raphe nucleus send projection fibers to the trigeminal sensory complex, and that some of them send their axons to both the principal sensory trigeminal nucleus and the caudal subdivision of the spinal trigeminal nucleus by way of axon collaterals. These projections may subserve suppression of the activity of nociceptive neurons in the trigeminal system.

Amidines↗

Serotoninergic projections from the dorsal raphe nucleus to the nucleus submedius in the rat and cat.

The nucleus submedius in the medial thalamus has been known to receive spinothalamic and trigeminothalamic fibers, and to contain neurons which can be activated by noxious stimuli. These previous findings suggest that the nucleus submedius may be involved in the processing and relay of pain-related information. In the present study, we immunohistochemically observed in the rat and cat that the nucleus submedius was distributed with a considerable amount of serotoninergic fibers. After iontophoretic injection of cholera toxin B subunit into the nucleus submedius, the sequential double-antigen immunofluorescence histochemistry for retrogradely transported cholera toxin B subunit and serotonin revealed that the serotoninergic fibers to the nucleus submedius arose mainly from the dorsal raphe nucleus, and additionally from the ventrolateral and medial parts of the midbrain periaqueductal gray. The direct projections from the dorsal raphe nucleus to the nucleus submedius were confirmed by anterograde axonal tracing after iontophoretic injection of Phaseolus vulgaris-leucoagglutinin into the dorsal raphe nucleus. The disappearance of almost all serotoninergic fibers in the nucleus submedius was also observed after destruction of the dorsal raphe nucleus. The fluorescent retrograde double-labeling with Diamidino Yellow and Fast Blue further revealed that some neurons in the dorsal raphe nucleus projecting directly to the nucleus submedius sent their axon collaterals to the ventrolateral orbital region of the cerebral cortex, nucleus accumbens, amygdala, nucleus raphe magnus, caudal spinal trigeminal nucleus, or spinal cord. The possible roles of the serotoninergic projections from the dorsal raphe nucleus to the nucleus submedius in pain control and/or the olfactolimbic functions are discussed.

Animals↗

Widespread dopaminergic projections of the subparafascicular thalamic nucleus in the rat.

The subparafascicular thalamic nucleus (Spf) contains a substantial number of dopaminergic neurons. The present study was designed to investigate in the rat whether or not Spf neurons projecting to a variety of central nervous system structures are dopaminergic. The following eight structures were tested for projection sites of Spf dopamine neurons: the neocortex, olfactory tubercle, nucleus accumbens, striatum, globus pallidus, amygdala, inferior olive, and spinal cord. By using a combination of fluorescent retrograde axonal tracing and immunofluorescence histochemistry for tyrosine hydroxylase, it has been revealed that the Spf provides a dopaminergic innervation, in varying degree, to each of these structures: the neocortex and spinal cord were the largest targets for dopaminergic projections from the Spf. The Spf was also found to contain significant numbers of dopaminergic neurons projecting to the olfactory tubercle and amygdala. In contrast, dopaminergic projections of Spf neurons to the nucleus accumbens, striatum, globus pallidus, and inferior olive were only minor. Furthermore, a series of fluorescent retrograde double-labeling experiments have indicated that individual Spf neurons are poorly collateralized to more than one of the eight terminal fields examined; the Spf neurons descending to the spinal cord relatively more frequently send axon collaterals ascending to the telencephalic structures, including the neocortex, olfactory tubercle, nucleus accumbens, striatum, and amygdala. The present results suggest that the Spf constitutes a major origin of widespread dopaminergic projections arising from the thalamus.

Animals↗

Deregulated c-fos modulates IgG2b production of B cells mediated by lipopolysaccharide.

We have examined effects of the deregulated c-fos protein on IgG2b production of B cells cultured with lipopolysaccharide (LPS) using splenic B cells from a transgenic line carrying the mouse c-fos gene under the control of the interferon alpha/beta (IFN) inducible Mx promoter (Mx-c-fosD). High c-fos expression was induced in the Mx-c-fosD B cells during the first two days of culture. DNA synthesis and IgG2b production were augmented in the culture. When IFN was added together with LPS, the high c-fos expression was prolonged until day 3 of culture. IgG2b production was remarkably suppressed. However, the production was not suppressed by upregulation of c-fos via exogenous IFN on day 4 of culture. These results suggest a regulatory effect of the c-fos protein on the differentiation of B cells to IgG2b producing cells at a distinct period.

Animals↗

Enhanced antitumor efficacy of a combination of CPT-11, a new derivative of camptothecin, and cisplatin against human lung tumor xenografts.

The objective of this study was to evaluate the antitumor efficacy of combined use of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and cisplatin (CDDP). The antitumor activities of CPT-11, CDDP and their combination against 3 human lung tumor xenografts were estimated using congenitally athymic BALB/c (nu/nu) mice. The doses were 47 mg/kg for CPT-11 and 6 mg/kg for CDDP on days 1, 5 and 9. In combination therapy, half of the single dosage of each agent was used. The doses were administered intraperitoneally. The antitumor activity and toxicity were evaluated in terms of the tumor volume and body weight change of mice, respectively. The combination therapy resulted in a statistically significant tumor regression compared to the use of only CPT-11 or CDDP in two tumor xenografts out of three. The toxicity of the combination therapy was no higher than that of CPT-11 or CDDP alone. These results suggest that the antitumor activity of the combination of CPT-11 and CDDP is superior to that of CPT-11 or CDDP alone.

Animals↗

The transport mechanism of an organic cation, disopyramide, by brush-border membranes. Comparison between renal cortex and small intestine of the rat.

The characteristics of disopyramide uptake in brush-border membrane vesicles isolated from rat renal cortex and small intestine were investigated. Transport of disopyramide into an osmotically reactive intravesicular space was observed with notable binding to the membrane surface. An outwardly directed H+ gradient stimulated disopyramide uptake, resulting in a transient uphill transport in both brush-border membranes. As for the renal brush-border membrane, the H+ gradient itself appeared to be the driving force for this stimulation of uptake. These findings suggest that disopyramide-H+ antiport is the mechanism of disopyramide action in renal cell membrane. The initial uptake was saturable (Km and Vmax of 68.0 microM and 1.25 nmol (mg protein)-1/30 s, respectively). The stimulation of disopyramide uptake by an outward H+ gradient in rat intestinal brush-border membrane was due to an interior negative H(+)-diffusion potential. A K(+)-diffusion potential (interior negative) enhanced disopyramide uptake. These results suggest that there are different mechanisms of disopyramide uptake for renal and intestinal brush-border membrane vesicles.

Animals↗

Bioavailability and diuretic effect of bumetanide following rectal administration of suppositories containing weak acids in human subjects.

The bioavailability of bumetanide following the oral administration of tablets, or the rectal administration of either macrogol suppositories or suppositories with and without weak acids were evaluated in human subjects. The absorption of bumetanide from those suppositories containing bumetanide without weak acids (control suppositories) was extremely poor, while the absorption from those suppositories containing citric acid or tartaric acid was enhanced. The mean area under the plasma concentration-time curve (AUC) following the rectal administration of the suppositories containing citric acid and tartaric acid was 52 and 62%, respectively, of that following the oral administration. On the other hand, the absorption rate constant (ka) and the mean residence time (MRT) following the rectal administration of the suppositories containing weak acids increased significantly compared to those administered orally. The time (Tmax) required to achieve the maximum plasma concentration (Cmax) in the plasma following the rectal administration of the suppositories containing weak acids was significantly shortened compared to the time of those administered orally. These results indicated that the bumetanide contained in the suppositories containing weak acids might be absorbed rapidly after administration. The diuretic effect of bumetanide following the oral and rectal administration was also evaluated. Sufficient diuretic effects were obtained following the rectal administration of the suppositories containing weak acids.

Administration, Oral↗

Enhanced absorption of bumetanide from suppositories containing weak acids in rabbits.

The in vitro release of bumetanide from macrogol suppositories with and without weak acids (citric acid and tartaric acid) was studied. The release of bumetanide was not affected when weak acids were added to the suppositories. The in vivo rectal absorption of bumetanide from the suppositories was evaluated in rabbits. The bioavailability (absolute), expressed as the ratio of the area under the plasma concentration-time curve (AUC) following oral administration of bumetanide, was 39% that of intravenous administration. The value in bumetanide following rectal administration of the suppositories without weak acids was 32%. Each absolute bioavailability following rectal administration of the suppositories with 5% citric acid and 5% tartaric acid was 52% and 42%, respectively. These values were significantly larger than those of rectal administration of the suppositories without weak acids. Particularly, the bioavailability following rectal administration of the suppositories containing citric acid was significantly different from even those of oral administration. The absorption rate constants of bumetanide from the suppositories with weak acids were significantly larger than those following oral administration. These results indicated the possibilities of the rectal route of administration of drugs which are weak organic acids and show low or variable bioavailability following oral administration.

Administration, Oral↗

[Neutrophil functions during treatment with granulocyte colony-stimulating factor (G-CSF) in the elderly with non-Hodgkin's lymphoma: including two patients accompanied with interstitial pneumonitis during the treatment with G-CSF].

We examined neutrophil functions in seven elderly patients with non-Hodgkin's lymphoma before and during treatment with granulocyte colony-stimulating factor (G-CSF) at the neutropenic stage after combination chemotherapy. Subcutaneous injection of 75 micrograms/d of G-CSF produced by E. coli was started when the neutrophil count decreased less than 1,500/microliter, and continued until the neutrophil count increased to about 10,000/microliter. The phagocytic activity of neutrophils from the elderly on day 3 of G-CSF treatment was markedly enhanced; 1,129.9 +/- 403 ps/100 PMNs, which was 185.7 +/- 31.4% (p < 0.001) as compared with that before G-CSF treatment. The neutrophil alkaline phosphatase (NAP) activity was also enhanced on day 3; 398.3 +/- 48 score, which was 135.2 +/- 5.1% (p < 0.001) as compared with that before G-CSF treatment. Two patients developed interstitial pneumonitis during or shortly after the treatment with G-CSF. Interstitial pneumonitis suddenly developed when their neutrophil count was increased, and the phagocytic activity and NAP activity recovered. The phagocytic activity of neutrophils from them was enhanced to 1,090 +/- 26 ps/100 PMNs and 772 ps/100 PMNs during the treatment with G-CSF, as compared with that before G-CSF treatment of 644 +/- 29 ps/100 PMNs and 465 +/- 69 ps/100 PMNs, respectively. The NAP activity was also enhanced to 372 from 264. One patient suffered from transient pulmonary dysfunction during the treatment with G-CSF. His neutrophil count was more than 13,000/microliter, and the phagocytic activity enhanced to 949 +/- 105 ps/100 PMNs. Dyspnea with suppressed PaO2 recovered reversibly after cessation of G-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗