Biomedical subjects

T Maeda

Publications and source records attributed to T Maeda.

At least 181 records · Page 10Linked to original sources

PubMed2000

Postnatal development of the dopaminergic neurons in the rat mesencephalon.

The two mesencephalic dopaminergic systems in the developing rat brain were investigated immunohistochemically by dopamine and tyrosine hydroxylase and the results were quantitatively analyzed with a computer. The number of the dopaminergic neurons in the substantia nigra and the ventral tegmentum area did not change significantly during the postnatal development. Dopaminergic terminals in the lateral septum peaked at postnatal days (PD) 30, when the cell size in middle third of the ventral tegmentum area which was suggested as an origin of this projection system, increased largely. Patchy structures in the striatum were shown most distinctly at PD 7 and disappeared at PD 35 using dopamine antibody, but there were no changes in the cell size of the substantia nigra from PD 14 to 75. Dopaminergic neurons, in general, do not show a transient change in ontogeny.

Age Factors↗

PubMed2000

Evaluation of the cytotoxic effects of bis-quaternary ammonium antimicrobial reagents on human cells.

The cytotoxic effects of newly synthesized bis-quaternary ammonium compounds (bis-QACs) and benzalkonium chloride were investigated on skin and blood cells, namely normal human epidermal keratinocytes of neonatal foreskin, a normal human skin fibroblast cell line NB1RGB, erythrocytes and a lymphoma cell line JM. The bis-QACs tested were 4, 4'-(1,6-hexamethylenedithio)bis(1-octylpyridinium iodide) (4DTBP-6, 8), N,N'-tetramethylenebis(1-dodecyl-4-carbamoylpyridinium iodide) (4BCAP-4,12), N,N'-hexamethylenebis(1-decyl-4-carbamoylpyridinium iodide) (4BCAP-6,10), 4,4'-(1,4-tetramethylenedicarbonyldiamine) bis (1-decylpyridinium iodide) (4DCABP-4,10), 4,4'-(1, 4-tetramethylenedicarbonyldiamine) bis (1-dodecylpyridinium iodide) (4DCABP-4,12), 4,4'-(1, 4-phenyldicarbonyldiamine)bis(1-dodecylpyridinium iodide) (4DCABP-P, 12), and 4,4'-(1, 6-hexamethylenedioxydicarbonyl)bis(1-dodecylpyridinium iodide) (4DOCBP-6,12). All bis-QACs consisted of two identical alkylpyridinium rings and bridge structure linking rings to each other have a methylene bridge but only 4DCABP-P,12 has a phenyl ring as a bridge. Most of the LD(50) values in acute cytotoxic assays of these bis-QACs tended to be lower than those of benzalkonium chloride. However, the comparison of the antibacterial activity against cytotoxic effects on several human cells revealed that bis-QACs, especially 4DTBP-6,8, have wide concentration ranges showing sufficient antibacterial activity and lower cytotoxic effect on human cells (except for 4DOCBP-6,12), although benzalkonium chloride caused significant human cell damage at the concentrations necessary for antibacterial activity. Moreover, judging from the LD(50) value of 4DTBP-6,8 [67 microM, a 6.7-fold higher concentration than the upper value of MIC] obtained in an artificial human skin model TESTSKIN, 4DTBP-6,8 is thought to be a more effective and safer antiseptic reagent for application to the skin surface than benzalkonium chloride. Taken together, bis-QACs are expected to be a promising new generation of antimicrobial QACs.

Anti-Bacterial Agents↗

PubMed2000

Transient nonketotic hyperglycinemia in an asphyxiated patient with pyridoxine-dependent seizures.

An asphyxiated neonate with pyridoxine-dependent seizures and associated transient nonketotic hyperglycinemia is reported. Frequent seizures and their resultant hypoxic-ischemic insult may have led to the elevation of the cerebrospinal fluid glycine level in this patient. Early diagnosis and treatment of pyridoxine-dependent seizures is essential for an improved neurologic outcome.

Asphyxia Neonatorum↗

PubMed2000

Ontogeny of (D-Ala(2))-deltorphin I-like immunoreactive neurones in foetal rat brain.

Foetal rat brain from embryonic day (ED) 12-22 was immunohistochemically studied to describe the time of first appearance and further distribution patterns of (D-Ala(2))-deltorphin-I-immunoreactive (DADTI-IR) nerve elements. The primary antiserum used in this study was a polyclonal antibody against DADTI previously used in adult and postnatal rat brain mapping. DADTI-IR nerve elements first appeared in the neuroepithelium of ventral mesencephalon on ED 13. From there, positive cell bodies migrated towards the mantle layer until they invaded the whole ventral mesencephalic tegmentum. They then reached their definitive position, corresponding to a subpopulation of the A8, A9 and A10 dopaminergic neurones that had been constantly observed also in the adult age. From ED 15-17, DADTI-positive nerve fibres appeared in the medial forebrain bundle, the neostriatum anlage, the accumbens nucleus, the olfactory tubercle, the fasciculus retroflexus, and the prefrontal cortex. All these locations have also been found in adult rats. From ED 14 onwards, transient DADTI-IR somata and nerve fibres were observed in retinal neuroepithelium, optic pathways as far as the superior colliculus, CA3 hippocampal field, reticular formation in the medulla oblongata. All these locations gradually disappeared either before birth (medulla oblongata) or within the first 3 weeks after birth. These results suggest that the DADT-like molecule recognised by our antibody has during the embryonic development a regulatory function in neuronal growth and differentiation.

Analgesics, Opioid↗

PubMed2000

Distribution of dopamine-immunoreactive fibers in the rat brainstem.

We describe the distribution of axons immunoreactive for dopamine in pons and medulla oblongata of rat under normal conditions or after inhibition of monoamine oxidase or dopamine beta-hydroxylase. In the pons of non-treated animal, fairly dense plexuses of dopamine-immunoreactive varicose fibers were found in the locus coeruleus, dorsal parabrachial and dorsal raphe nuclei, central gray and reticular formation dorsal to the superior olive. In the medulla oblongata, the immunoreactive fibers were abundant in the dorsal vagal complex, lateral paragigantocellular nucleus, midline raphe nuclei and spinal trigeminal nucleus. Monoamine oxidase inhibition made it possible to increase the intensity of immunoreactivity and consequently the number of labeled fibers in these areas, indicating that dopamine is perpetually oxidized by monoamine oxidase, and consequently in low concentration under normal conditions. Sparse dopamine-immunoreactive fibers were observed in the pontine gray, motor trigeminal nucleus, inferior olive and major axon bundles such as the dorsal and ventral tegmental bundles, where numerous noradrenergic fibers have been reported. In axons of these areas, intense dopamine-immunoreactivity was seen only after inhibition of dopamine-beta-hydroxylase. It appears that dopamine is released and oxidized in response to autonomic changes such as hypoxia, hemorrhage, and cardiovascular variation in the caudal brainstem, as we have described elsewhere.

Animals↗

PubMed2000

The locus coeruleus: history.

The author outlines the history of the locus coeruleus from its discovery to the latest research findings. Although Russel's report in Texas has been believed to be the first break-through scientific article of this neuronal structure, there were two preceding, anatomical and physiological, studies made by Japanese groups. One of the aims of this review is to shed brief light on their works, which being written in Japanese so that might have been unfamiliar to most researchers in the world.

Anatomy↗

PubMed2000

Antiepileptic effect of nefiracetam on kainic acid-induced limbic seizure in rats.

Nefiracetam is being studied as a novel cognition-enhancing agent; however, it has been suggested from studying its chemical structure that it has a potential anticonvulsive effect. We examined the antiepileptic effect of nefiracetam on kainic acid (KA)-induced seizures. KA was infused into the left basolateral amygdaloid nucleus and focal limbic seizures were induced in 43 male Wistar rats. During status epilepticus, 10, 50, 100 or 200 mg/kg of nefiracetam was intravenously injected. Nefiracetam inhibited KA-induced limbic seizures at doses over 100 mg/kg while it had a sedative effect on the animals. In (14C) deoxyglucose autoradiographic studies, the propagation of seizure-induced hypermetabolic areas was also suppressed dose-dependently. From the results, it was indicated that nefiracetam has an antiepileptic effect and that its application may suppress seizure propagation. Further study is required, whether this agent is available as a novel anticonvulsant.

Animals↗

PubMed2000

Effects of light on the tritrophic interaction between kidney bean plants, two-spotted spider mites and predatory mites, Amblyseius womersleyi (Acari: Phytoseiidae).

By analyzing the volatiles from Tetranychus urticae-infested kidney bean plants (Phaseolus vulgaris) at different times for two days, we found that they were mainly produced in the light. Tetranychus urticae showed a higher oviposition rate and spent more time feeding during the day (in the light) than at night (in the dark). Infested leaves placed in the light attracted the predatory mite Amblyseius womersleyi, whereas those that were placed in the dark for at least 2 h in daytime did not. This indicates that presence or absence of light affects the production of herbivore-induced plant volatiles. Amblyseius womersleyi dispersed more frequently and consumed more T. urticae eggs during the day (in the light) than at night (in the dark), whereas their oviposition rate did not differ between day and night. Presence or absence of herbivore-induced plant volatiles in the surroundings did not affect dispersal, predation or oviposition rates of A. womersleyi. These results show that A. womersleyi's behavior coincides with the production pattern of herbivore-induced plant volatiles.

Animals↗

PubMed2000

Lactacystin activates FLICE (caspase 8) protease and induces apoptosis in Fas-resistant adult T-cell leukemia cell lines.

Lactacystin (LC) is a specific inhibitor of the proteasome, and has recently been shown to induce apoptosis in certain cell lines. In the present study, we established Fas-resistant adult T-cell leukemia (ATL) cell subclones RSO4 and RST1 from their parental Fas-sensitive cell lines SO4 and ST1, and examined whether LC can overcome Fas resistance. LC completely inhibited proteasome function as determined by a peptidyl-MCA substrate (LLVY-MCA and LLE-MCA), and induced apoptosis in these cell lines irrespective of Fas sensitivity at low concentrations (approximately 10 microM). LC induced the activation of caspase 3 (CPP32/Yama) and caspase 6 proteases in an identical manner to Fas-mediated apoptosis. Moreover, LC induced the activation of caspase 8 (FLICE) protease, which is the initiator of the Fas-mediated apoptotic cascade. Synthesized proteasome inhibitory peptide MG-115 (ZLLnV-CHO) also induced apoptosis in these cell lines. These results indicated that proteasome inhibitors overcome Fas-resistance by bypassing the proximal part of the Fas signal. Inhibition of the proteasome function may be a new strategy for the treatment of ATL.

Acetylcysteine↗

PubMed2000

Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation.

The composite structure of the mammalian skull, which forms predominantly via intramembranous ossification, requires precise pre- and post-natal growth regulation of individual calvarial elements. Disturbances of this process frequently cause severe clinical manifestations in humans. Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans. Here we show that Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis, and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina (PFM). Msx2-/- mice also have defects in endochondral bone formation. In the axial and appendicular skeleton, post-natal deficits in Pth/Pthrp receptor (Pthr) signalling and in expression of marker genes for bone differentiation indicate that Msx2 is required for both chondrogenesis and osteogenesis. Consistent with phenotypes associated with PFM, Msx2-mutant mice also display defective tooth, hair follicle and mammary gland development, and seizures, the latter accompanied by abnormal development of the cerebellum. Most Msx2-mutant phenotypes, including calvarial defects, are enhanced by genetic combination with Msx1 loss of function, indicating that Msx gene dosage can modify expression of the PFM phenotype. Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis.

Abnormalities, Multiple↗

PubMed2000

Histologic transformation of follicular lymphoma after allogeneic bone marrow transplantation.

A 38-year-old man with refractory follicular lymphoma underwent allogeneic BMT from an HLA-identical sibling donor. He had generalized lymphadenopathy, hepatosplenomegaly and lymphoma infiltration of the marrow, all of which disappeared within 3 months following transplantation. Six months post-transplant, progressive hepatomegaly developed in the absence of splenomegaly and lymphadenopathy, and he died from hepatic failure. Autopsy disclosed diffuse large B cell lymphoma of the liver, into which the follicular lymphoma had transformed. Future issues to be investigated should include the optimal timing of allogeneic BMT for low-grade lymphomas.

Adult↗

PubMed2000

Protective immunity is induced in murine colon carcinoma cells by the expression of interleukin-12 or interleukin-18, which activate type 1 helper T cells.

We investigated the antitumor effects induced by the production of interleukin-12 (IL-12) or IL-18, which influence the function of T helper type 1 cells, in murine colon carcinoma cells (Colon 26). Retrovirally transduced cells with IL-12 genes that encoded both p35 and p40 (Colon 26/IL-12) lost their tumorigenicity when inoculated subcutaneously or intraperitoneally into syngeneic immunocompetent mice. Moreover, the mice that had rejected the Colon 26/IL-12 cells generated protective immunity to wild-type (wt) cells when subsequently challenged. Colon 26 cells transduced with the IL-18 gene (Colon 26/IL-18) could not form subcutaneous tumors in immunocompetent mice, and the mice became resistant to inoculated wt cells. Immunohistochemical analysis revealed that the numbers of blood vessels in Colon 26/IL-12 or Colon 26/IL-18 tumors were markedly reduced, and that the expression of adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 increased on the endothelium in the stroma of Colon 26/IL-12 tumors. The loss of tumorigenicity of Colon 26/IL-12 or Colon 26/IL-18 cells was not observed in immunocompromised mice. However, the survival days of the immunocompromised mice inoculated with Colon 26/IL-12 but not Colon 26/IL-18 cells were significantly longer than those inoculated with wt cells. The secretion of cytokines that stimulate T helper type 1 cells from tumor cells can thereby induce an antitumor response. However, the effector cells involved in these antitumor effects could differentially migrate to the tumors, and the inhibition of angiogenesis may partially contribute to the antitumor responses observed.

Animals↗

PubMed2000

Transduction of murine colon carcinoma cells with interleukin-15 gene induces antitumor effects in immunocompetent and immunocompromised hosts.

We examined the antitumor effects caused by murine colon carcinoma cells (Colon 26) transduced with interleukin-15 (IL-15) gene. Although the in vitro proliferation rate of IL-15-secreting Colon 26 (Colon 26/IL-15) cells was not different from that of wild-type (wt) cells, small subcutaneous tumors of Colon 26/IL-15 cells that developed in syngeneic immunocompetent mice regressed spontaneously in contrast to tumors of wt cells. The mice that had eliminated tumors of Colon 26/IL-15 cells rejected wt cells when subsequently challenged. The survival of the mice that had been inoculated intraperitoneally with Colon 26/IL-15 cells was significantly prolonged compared with that of the mice injected with wt cells. However, in an experimental lung metastasis model, the survival of the mice inoculated with Colon 26/IL-15 cells remained the same as that of the mice inoculated with wt cells. The inoculation of Colon 26/IL-15 cells into immunocompromised nude or severe combined immunodeficient mice produced tumors, but the survival of the immunocompromised mice was significantly longer than that of the mice inoculated with wt cells. The nude mice inoculated with Colon 26/IL-15 cells also survived longer than the severe combined immunodeficient mice with Colon 26/IL-15 cells. Depletion of natural killer cells in nude mice with anti-asialo GM1 antibody did not influence the survival of the mice injected with Colon 26/IL-15 cells. Immunohistological examination revealed that CD31+ cells migrated into tumors of Colon 26/IL-15 cells that developed in immunocompetent and immunocompromised mice. Taken together, our results indicate that an inoculation of IL-15-producing tumor cells can produce antitumor effects that are mediated by a variety of immunocompetent cells.

Animals↗

PubMed2000

Compound heterozygous group A xeroderma pigmentosum patient with a novel mutation and an inherited reciprocal translocation.

The severity of neurological abnormalities in Japanese group A xeroderma pigmentosum (XP-A) patients correlates with the sites of non-sense mutation in the XP-A gene. We describe a patient who presented with a more severe photosensitivity and neurological abnormality than those in typical Japanese XP-A patients with a splicing mutation in intron 3. The patient was compound heterozygous for the splicing mutation in intron 3, which resulted in formation of a non-sense codon in exon 4, and a novel non-sense mutation at codon 208 in exon 5, a C to T transition creating a stop codon TAG. Although the combination of these mutations might have been thought to cause only mild neurological signs, the longer truncated XP-A proteins than those of typical XP-A patients may have resulted in severe neurological symptoms. This phenomenon may be explained by a translocation of chromosome (1;10)(q25.3;q22.3) inherited from his father.

Adult↗

PubMed2000

Reserpine pretreatment prevents increases in extracellular striatal dopamine following L-DOPA administration in rats with nigrostriatal denervation.

The influence of L-DOPA and reserpine on extracellular dopamine (DA) levels in the striatum of intact and dopaminergic denervated rats was studied using the brain microdialysis technique. In intact rats, reserpine (5 mg/kg s.c.) reduced extracellular DA levels to 4% of basal values. L-DOPA (50 mg/kg i.p.) had no effect on extracellular DA levels in reserpine-pretreated rats. In rats with 6-hydroxydopamine-induced lesion of the nigrostriatal dopaminergic system, basal levels of extracellular DA were low but markedly increased by L-DOPA (50 mg/kg i.p.). In 6-hydroxydopamine-lesioned rats, pretreatment with reserpine (5 mg/kg s.c.) diminished L-DOPA (50 mg/kg i.p.)-induced increases in extracellular DA levels to 16% of those obtained in denervated animals not pretreated with reserpine (p<0.01). These results suggest that in the intact striatum, extracellular DA stems mainly from vesicular storage sites and that in the striatum with dopaminergic denervation, a large part of the L-DOPA-derived extracellular DA is also derived from a vesicular pool that is released by an exocytosis mechanism.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Analysis of the arterial blood pressure waveform using Fast Fourier Transform technique during left ventricular nonpulsatile assistance: in vitro study.

The arterial blood pressure waveform is variable during left ventricular assistance. The aim of this study is to examine the correlation between the left ventricular assist device (LVAD) condition and the arterial blood pressure waveform in a fixed cardiac output condition using a mock circuit. This mock circulation loop was composed of an aortic compliance chamber, a left atrial compliance chamber, a pneumatic pulsatile pump as a native heart, and a rotary blood pump representing the LVAD with left atrial drainage. The Fast Fourier Transform technique was utilized to analyze the arterial blood pressure waveform and calculate the pulsatility index (PI) and the pulse power index (PPI). The PI and PPI decreased with the increase of the LVAD rotational speed, exponentially. There was a significant negative correlation between the PI, PPI, and the LVAD rotational speed, flow rate, and assist ratio. The best correlation was observed between the PPI and the assist ratio (r = 0.986). From this viewpoint, an ideal LVAD condition may be estimated from the pulsatility change of the arterial blood pressure waveform.

Blood Pressure↗

PubMed2000

Right ventricular assist system feedback flow control parameter for a rotary blood pump.

At least 25-30% of patients with a permanent implantable left ventricular assist device (LVAD) experience right ventricular failure; therefore, an implantable biventricular assist system (BiVAS) with small centrifugal pumps is being developed. Many institutions are focusing and developing a control system for a left ventricular assist system (LVAS) with rotary blood pumps. These authors feel that the right ventricular assist system (RVAS) with rotary blood pumps should be developed simultaneously. A literature search indicated no recent reports on the effect of hemodynamics and exercise with this type of nonpulsatile implantable RVAS. In this study, a calf with an implantable right ventricular assist system (RVAS) was subjected to 30 min of exercise on a treadmill at 1.5 mph, resulting in excellent hemodynamics. The input voltage remained unchanged. Hemodynamic recordings were taken every 5 min throughout the testing period, and blood gas analysis was done every 10 min. Oxygen uptake (VO2), oxygen delivery (DO2), and oxygen extraction (O2ER) were calculated and analyzed. Two different pump flows were investigated: Group 1 low assist (<3.5 L/min) and Group 2 high assist (>3.5 L/min). In both groups, the RVAS flow rates were unchanged while the pulmonary artery (PA) flow increased during exercise; also, the heart rate and right atrial pressure (RAP) increased during exercise. There were no significant differences in the 2 groups. The PA flow correlates to the heart rate during exercise. In all of the tests, the VO2 and DO2 increased during exercise. Regarding VO2, no changes were observed during the different flow conditions; however, the DO2 of Group 2 was higher than that of Group 1. Because the implantable RVAS did not have pump flow changes during the test conditions, it was necessary to incorporate a flow control system for the implantable RVAS. During exercise with an implantable RVAS rotary blood pump, incorporating the heart rate and VO2 as feedback parameters is feasible for controlling the flow rate.

Animals↗

PubMed2000

Gyro pump wear and deformation analysis in vivo study: creep deformation.

The Gyro pump has a double pivot bearing system to support its impeller. In this study, the integrity of the bearing system was examined after ex vivo studies. The pumps were implanted into calves and evaluated for different periods as a paracorporeal left ventricular assist device (LVAD). One pump was subjected to a test of 30 days, 1 for 15 days, 4 for 14 days, 1 for 10 days, 1 for 7 days, 2 for 4 days, and 4 for 2 days. One additional pump was subjected to percutaneous cardiopulmonary support (PCPS) condition for 6 days (total pressure head 500 mm Hg with a pump flow rate of 3 L/min). The anticoagulation treatment consisted of a continuous administration of heparin to maintain an achieved clotting time (ACT) of 200-250 s during the LVAD study and 250-300 s during the PCPS study. After the experiment, the pumps were disassembled, and the wear and deformation of male and female bearings were analyzed. There were no dimensional changes on male bearings but there were on female bearings. Wear and deformation of the female bearings were calculated as follows: wear and deformation = (depth of female before pumping) - (depth after pumping). Thirteen assembled Gyro pumps were disassembled to measure the depth of the female bearings before pumping. There was no statistical relationship between the wear and deformation and the motor speed x driving period. From these results, the deformation was not due to wear but to the creep or elastic deformation. This study suggested that the double pivot bearing system of the Gyro pump is highly durable.

Animals↗