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Biomedical subjects

F Murakami

Publications and source records attributed to F Murakami.

At least 19 recordsLinked to original sources
PubMed2005

Acquired symmetrical dermal melanocytosis (naevus of Hori) developing after aggravated atopic dermatitis.

BACKGROUND: Acquired symmetrical dermal melanocytosis (ASDM) is a pigmentary disorder characterized by blue-brown macules most frequently seen on the face of young and middle-aged Asian women. ASDM developing after other skin diseases has not been previously reported. OBJECTIVES: To characterize the clinical and histopathological features of ASDM associated with atopic dermatitis (AD) and to elucidate the differences between AD-associated ASDM and idiopathic ASDM. METHODS: Sixteen patients with ASDM associated with AD were examined clinically and histopathologically and were compared with 69 patients with idiopathic ASDM. RESULTS: The AD patients associated with ASDM consisted of four men and 12 women with a mean age of 32.8 +/- 13.1 years. Most patients remembered that the pigmented macules appeared in places where refractory eczema had existed for a long time. The marked preponderance in females and the appearance in the early reproductive period were common features of AD-associated ASDM and idiopathic ASDM. AD-associated ASDM was most commonly observed on the forehead (68.8%) and on the backs of the hands (50.0%), whereas 89.9% of idiopathic ASDM was seen on the cheeks. There was no significant difference in the number of dermal melanocytes between AD-associated ASDM and idiopathic ASDM. Electron microscopic studies demonstrated many mature melanocytes and smaller numbers of immature melanocytes in the dermis. Some melanocytes were seen adjacent to mast cells. CONCLUSIONS: AD-associated ASDM does not appear to be rare in Japan. ASDM may be triggered in AD patients by sunlight exposure, some alterations in sex hormones and/or persistent cutaneous inflammation. Histamine and stem cell factor produced by mast cells may play crucial roles in the pathogenesis of AD-associated ASDM.

Adult↗
PubMed2001

Light and electron microscopic study of corticorubral synapses in adult cat: evidence for extensive synaptic remodeling during postnatal development.

Spine-like dendritic protrusions (SLDPs) emanating from developing dendrites have been proposed to play an important role in early synaptogenesis. We previously analyzed synaptic termination sites on soma-dendritic membrane of newborn cats and found that corticorubral (CR) axons form synapses preferentially on SLDPs (Saito et al., 1997). In the present study, we examined CR synapses in adult cats to elucidate the maturation process of CR synapses in relation to SLDPs. Electron microscopic observation of serial thin sections of Phaseolus vulgaris-leucoagglutinin-labeled axons revealed that approximately 60% of CR terminals in adult cats formed synapses on dendritic spines. We also found that CR axons terminate on dendritic spines originating from the intermediate or distal dendrites of rubrospinal cells (more than 200 microm apart from the soma), in contrast to kittens in which CR fibers terminate on SLDPs originating from the proximal dendrites (less than 100 microm apart from the soma) of rubrospinal cells (Saito et al. [1997] J. Neurosci. 17:8792-8803). These results suggest that CR synapses undergo remarkable remodeling after initial termination on SLDP during postnatal development.

Aging↗
PubMed2001

Crossing the floor plate triggers sharp turning of commissural axons.

During development of the vertebrate CNS, commissural axons initially grow circumferentially toward the ventral midline floor plate. After crossing the floor plate, they abruptly change their trajectory from the circumferential to the longitudinal axis. Although recent studies have unraveled the mechanisms that control navigation of these axons along the circumferential axis, those that result in the transition from circumferential to longitudinal trajectory remain unknown. Here, we examined whether an interaction with the floor plate is a prerequisite for the initiation of trajectory transition of commissural axons, using in vitro preparations of the rat metencephalon. We found that commissural axons in the metencephalon, once having crossed the floor plate, turned sharply to grow longitudinally. In contrast, axons extending in floor plate-deleted preparations, continued to grow circumferentially, ignoring the hypothetical turning point. These results suggest that a prior interaction of commissural axons with floor plate cells is a key step for these axons to activate a navigation program required for their change in axonal trajectory from the circumferential to the longitudinal axis.

Animals↗
PubMed2001

Visualization, direct isolation, and transplantation of midbrain dopaminergic neurons.

To visualize and isolate live dopamine (DA)-producing neurons in the embryonic ventral mesencephalon, we generated transgenic mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene promoter. In the transgenic mice, GFP expression was observed in the developing DA neurons containing tyrosine hydroxylase. The outgrowth and cue-dependent guidance of GFP-labeled axons was monitored in vitro with brain culture systems. To isolate DA neurons expressing GFP from brain tissue, cells with GFP fluorescence were sorted by fluorescence-activated cell sorting. More than 60% of the sorted GFP(+) cells were positive for tyrosine hydroxylase, confirming that the population had been successfully enriched with DA neurons. The sorted GFP(+) cells were transplanted into a rat model of Parkinson's disease. Some of these cells survived and innervated the host striatum, resulting in a recovery from Parkinsonian behavioral defects. This strategy for isolating an enriched population of DA neurons should be useful for cellular and molecular studies of these neurons and for clinical applications in the treatment of Parkinson's disease.

Animals↗
PubMed2001

HBV-related fulminant hepatic failure: successful intensive medical therapy in a candidate for liver transplantation.

Fulminant hepatic failure (FHF) usually has a fatal prognosis without liver transplantation. We describe the case of a woman who developed FHF, and was evaluated as a candidate for liver transplantation, but who was cured without transplantation through intensive medical care that included glucagon-insulin therapy, methylprednisolone pulse therapy, interferon beta and lamivudine administration, cyclosporine administration, and high-volume hemodiafiltration and plasma exchange. In a patient with FHF who is a candidate for liver transplantation but for whom the transplantation cannot be performed for some reason, intensive medical therapy, including regeneration-promoting therapy, immunosuppressive therapy, antiviral therapy, and vigorous hepatic support, should be carried out.

Antiviral Agents↗
PubMed2001

The release of the substrate for xanthine oxidase in hypertensive patients was suppressed by angiotensin converting enzyme inhibitors and alpha1-blockers.

OBJECTIVE: Hyperuricemia is associated with the vascular injury of hypertension, and purine oxidation may play a pivotal role in this association, but the pathophysiology is not fully understood. We tested the hypothesis that in hypertensive patients, the excess amount of the purine metabolite, hypoxanthine, derived from skeletal muscles, would be oxidized by xanthine oxidase, leading to myogenic hyperuricemia as well as to impaired vascular resistance caused by oxygen radicals. METHODS: We investigated the production of hypoxanthione, the precursor of uric acid and substrate for xanthine oxidase, in hypertensive patients and found that skeletal muscles produced hypoxanthine in excess. We used the semi-ischemic forearm test to examine the release of hypoxanthine (deltaHX), ammonium (deltaAmm) and lactate (deltaLAC) from skeletal muscles in essential hypertensive patients before (UHT: n = 88) and after treatment with antihypertensive agents (THT: n = 37) in comparison to normotensive subjects (NT: n = 14). RESULTS: deltaHX, as well as deltaAmm and deltaLAC, were significantly higher in UHT and THT (P< 0.01) than in NT. This release of deltaHX from exercising skeletal muscles correlated significantly with the elevation of lactate in NT, UHT and THT (y = 0.209 + 0.031x; R2 = 0.222, n = 139: P < 0.01). Administration of doxazosin (n = 4), bevantolol (n = 5) and alacepil (n = 8) for 1 month significantly suppressed the ratio of percentage changes in deltaHX by -38.4 +/- 55.3%, -51.3 +/- 47.3% and -76.3 +/- 52.2%, respectively (P< 0.05) but losartan (n = 3), atenolol (n = 7) and manidipine (n = 10) did not reduce the ratio of changes; on the contrary, they increased it in deltaHX by +188.2 +/- 331%, +96.2 +/- 192.2% and +42.6 +/- 137.3%, respectively. The elevation of deltaHX after exercise correlated significantly with the serum concentration of uric acid at rest in untreated hypertensive patients (y = 0.194 - 0.255x; R2 = 0.185, n = 30: P < 0.05). The prevalence of reduction of both deltaHX and serum uric acid was significantly higher in the patients treated with alacepril, bevantolol and doxazosin (67%: P < 0.02) than in the patients treated with losartan, atenolol and manidipine (12%). CONCLUSIONS: It is concluded that the skeletal muscles of hypertensive patients released deltaHX in excess by activation of muscle-type adenosine monophosphate (AMP) deaminase, depending on the degree of hypoxia. The modification of deltaHX by angiotensin-converting enzyme inhibitors and alpha1-blockers influenced the level of serum uric acid, suggesting that the skeletal muscles may be an important source of uric acid as well as of the substrate of xanthine oxidase in hypertension.

AMP Deaminase↗
PubMed2001

Excitatory postsynaptic potentials trigger a plateau potential in rat subthalamic neurons at hyperpolarized states.

The subthalamic nucleus (STN) directly innervates the output structures of the basal ganglia, playing a key role in basal ganglia function. It is therefore important to understand the regulatory mechanisms for the activity of STN neurons. In the present study, we aimed to investigate how the intrinsic membrane properties of STN neurons interact with their synaptic inputs, focusing on their generation and the properties of the long-lasting, plateau potential. Whole cell recordings were obtained from STN neurons in slices prepared from postnatal day 14 (P14) to P20 rats. We found that activation of glutamate receptor-mediated excitatory synaptic potentials (EPSPs) evoked a plateau potential in a subpopulation of STN neurons (n = 13/22), in a voltage-dependent manner. Plateau potentials could be induced only when the cell was hyperpolarized to more negative than about -75 mV. Plateau potentials, evoked with a depolarizing current pulse, again only from a hyperpolarized state, were observed in about half of STN neurons tested (n = 162/327). Only in neurons in which a plateau potential could be evoked by current injection did EPSPs evoke plateau potentials. L-type Ca(2+) channels, Ca(2+)-dependent K(+) channels, and TEA-sensitive K(+) channels were found to be involved in the generation of the potential. The stability of the plateau potential, tested by the injection of a negative pulse current during the plateau phase, was found to be robust at the early phase of the potential, but decreased toward the end. As a result the early part of the plateau potential was resistant to membrane potential perturbations and would be able to support a train of action potentials. We conclude that excitatory postsynaptic potentials, evoked in a subpopulation of STN neurons at a hyperpolarized state, activate L-type Ca(2+) and other channels, leading to the generation of a plateau potential. Thus about half of STN neurons can transform short-lasting synaptic excitation into a long train of output spikes by voltage-dependent generation of a plateau potential.

2-Amino-5-phosphonovalerate↗
PubMed2001

Local nonpermissive and oriented permissive cues guide vestibular axons to the cerebellum.

Information that originates from peripheral sensory organs is conveyed by axons of cephalic sensory cranial ganglia connecting the sensory organs to appropriate central targets in the brain. Thus, the establishment of correct axonal projections by sensory afferents is one of the most important issues in neural development. Previously, we examined the development of the vestibular nerve that originates from the VIIIth ganglion using a flat whole-mount preparation of the rat hindbrain and developed an in vitro, culture preparation that can recapitulate vestibular nerve development (Tashiro, Y., Endo, T., Shirasaki, R., Miyahara, M., Heizmann, C. W. and Murakami, F. (2000) J. Comp. Neurol. 417, 491-500). Both in vivo and in vitro, the ascending branch of the VIIIth ganglion projecting to the cerebellum reaches the base of the cerebellar primordium and starts to splay out towards the rhombic lip, apparently avoiding the ventral metencephalon. We now examine the nature of cues that guide vestibulocerebellar axons by applying various manipulations to the flat whole-mount in vitro preparation. Our observations suggest that local nonpermissive cues and oriented cues play a pivotal role in the guidance of vestibular axons to their central target.

Afferent Pathways↗
PubMed2000

Inhibitory mechanism by polysialic acid for lamina-specific branch formation of thalamocortical axons.

During development, thalamocortical axons form arbors primarily in layer 4 of the neocortex. This lamina-specific branch formation was studied in cultures of rat thalamic explants grown next to chemically fixed cortical slices. After a week in vitro, thalamic axons formed branches specifically in the target layer of fixed cortical slices, regardless of the orientation of the ingrowth. This in vitro system permits a direct assessment of contributions of membrane-associated molecules to thalamic axon branch formation. To this end, the present study uses three enzymatic perturbations: chondroitinase, phosphatidylinositol phospholipase C, or the polysialic acid (PSA)-specific endoneuraminidase (endo N). With endo N pretreatment of cortex, the number of branch points was increased significantly, whereas branch tip length was decreased. In addition, the localization of branch points to the target layer was weakened considerably. These features of branch formation were not altered by the other two enzymatic treatments, except that branch tips were shortened by chondroitinase treatment to the same extent as in endo N treatment. These results suggest that membrane-bound components are involved in lamina-specific branch formation of thalamocortical axons, and in particular that PSA moieties contribute to laminar specificity by inhibiting branch emergence in inappropriate layers.

Animals↗
PubMed2000

Dorsal spinal cord inhibits oligodendrocyte development.

Oligodendrocytes are the myelinating cells of the mammalian central nervous system. In the mouse spinal cord, oligodendrocytes are generated from strictly restricted regions of the ventral ventricular zone. To investigate how they originate from these specific regions, we used an explant culture system of the E12 mouse cervical spinal cord and hindbrain. In this culture system O4(+) cells were first detected along the ventral midline of the explant and were subsequently expanded to the dorsal region similar to in vivo. When we cultured the ventral and dorsal spinal cords separately, a robust increase in the number of O4(+) cells was observed in the ventral fragment. The number of both progenitor cells and mature cells also increased in the ventral fragment. This phenomenon suggests the presence of inhibitory factor for oligodendrocyte development from dorsal spinal cord. BMP4, a strong candidate for this factor that is secreted from the dorsal spinal cord, did not affect oligodendrocyte development. Previous studies demonstrated that signals from the notochord and ventral spinal cord, such as sonic hedgehog and neuregulin, promote the ventral region-specific development of oligodendrocytes. Our present study demonstrates that the dorsal spinal cord negatively regulates oligodendrocyte development.

Animals↗
PubMed2000

The mode of actions of lysozyme as an immunoglobulin production stimulating factor.

As we demonstrated before, hen egg white lysozyme stimulates immunoglobulin production by a human-human hybridoma line, HB4C5 cells and human peripheral blood lymphocytes. Then, the mode of actions of lysozyme as an immunoglobulin production stimulating factor was investigated. The immunoglobulin production stimulating activity of lysozyme was inactivated by trypsin digestion, even though the enzymatic activity was completely preserved. This fact suggests that the immunoglobulin production stimulating effect of lysozyme is irrelevant to its enzymatic function. Furthermore, this means that the effect is a novel function of this enzyme. Lysozyme enhanced IgM production by transcription-suppressed HB4C5 cells treated with actinomycin D. However, the enzyme was ineffective to accelerate IgM production by translation-suppressed HB4C5 cells treated with cycloheximide or sodium fluoride. In addition, the intracellular IgM content of HB4C5 cells treated with monensin for suppression of the post-transcription activity was obviously increased by lysozyme, although the secretion of IgM was inhibited. These findings suggest that lysozyme accelerates the translation process to enhance immunoglobulin productivity.

Animals↗
PubMed2000

Local directional cues control growth polarity of dopaminergic axons along the rostrocaudal axis.

The vertebrate CNS is composed of a variety of longitudinal axonal tracts extending rostrally and caudally. Although recent studies have demonstrated that chemoattraction and chemorepulsion play key roles in axon guidance along the circumferential axis in the neural tube of the vertebrate, mechanisms of axonal elongation along the longitudinal axis, and most importantly, what determines rostrocaudal polarity of axonal growth, remains unknown. Here, we examined the mechanism that guides midbrain dopaminergic axons rostrally, using flat whole-mount preparations of embryonic rat brain both in vivo and in vitro. At embryonic day 11 (E11) and early stage E12, dopaminergic neurons in the ventral midbrain extended short axons dorsally. By middle stage E12, these axons had increased in number, some deflecting rostrally and others caudally. At E13, almost all axons showed rostrally oriented growth heading toward the forebrain targets. In in vitro whole-mount preparations prepared from an E12 embryo and cultured for 24 hr, these axons showed rostrally oriented growth, but when they were forced to grow on substratum of reversed rostrocaudal polarity, they turned abruptly and grew following the polarity of the reversed midbrain substratum. These results suggest that local directional cues in the midbrain guide these axons rostrally and support the idea that substratum-associated polarized cues play an important role in axon guidance along the longitudinal axis.

Animals↗
PubMed2000

Afferents of cranial sensory ganglia pathfind to their target independent of the site of entry into the hindbrain.

In vertebrates, sensory neurons interconnect a variety of peripheral tissues and central targets, conveying sensory information from different types of sensory receptors to appropriate second-order neurons in the central nervous system (CNS). To explore the possibility that the different rhombomere environments where sensory neurons enter into the hindbrain affect the pathfinding capability of growth cones, we studied the development of the VIIIth ganglion afferent both in vivo and in vitro. We focused on the vestibular nerve because it is the only cranial nerve projecting to the cerebellum, allowing for ready identification from its pattern of projection. Embryonic rat brain was cut along the dorsal midline and, with the VIIIth and Vth ganglia still attached, flat mounted and visualized with antibodies specific for sensory ganglia. Axons reached the cerebellar primordium at embryonic day (E) 13, then splayed out towards the edges of the rhombic lip of rostral hindbrain. In vitro, the VIIIth ganglion showed development similar to that in vivo and innervated the cerebellum, an appropriate target, indicating that mechanisms for axon guidance and target recognition are preserved in vitro. When the VIIIth ganglion was transplanted to the position of the Vth ganglion, axons from the transplanted ganglion entered the cerebellar primordium with a trajectory characteristic of the VIIIth nerve. These results indicate that the central projection pattern of the VIIIth nerve is not affected by the environment of nerve entry into the brainstem, suggesting that axons of sensory cranial ganglion intrinsically possess the capacity to find their target correctly.

Afferent Pathways↗
PubMed2000

Characterization of factors regulating lamina-specific growth of thalamocortical axons.

During development, most thalamocortical axons extend through the deep layers to terminate in layer 4 of neocortex. To elucidate the molecular mechanisms that underlie the formation of layer-specific thalamocortical projections, axon outgrowth from embryonic rat thalamus onto postnatal neocortical slices which had been fixed chemically was used as an experimental model system. When the thalamic explant was juxtaposed to the lateral edge of fixed cortical slice, thalamic axons extended farther in the deep layers than the upper layers. Correspondingly, thalamic axons entering from the ventricular side extended farther than those from the pial side. In contrast, axons from cortical explants cultured next to fixed cortical slices tended to grow nearly as well in the upper as in the deep layers. Biochemical aspects of lamina-specific thalamic axon growth were studied by applying several enzymatic treatments to the cortical slices prior to culturing. Phosphatidylinositol phospholipase C treatment increased elongation of thalamic axons in the upper layers without influencing growth in the deep layers. Neither chondroitinase, heparitinase, nor neuraminidase treatment influenced the overall projection pattern, although neuraminidase slightly decreased axonal elongation in the deep layers. These findings suggest that glycosylphosphatidylinositol-linked molecules in the cortex may contribute to the laminar specificity of thalamocortical projections by suppressing thalamic axon growth in the upper cortical layers.

Animals↗
PubMed2000

A factor XI deficiency associated with a nonsense mutation (Trp501stop) in the catalytic domain.

We identified a novel mutation in an asymptomatic 65-year-old Japanese man with severe factor XI deficiency. Sequence analysis after polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP) analysis of his factor XI gene revealed a G-->A transition in codon 501 of exon 13, resulting in a substitution of Trp501 (TGG) by a stop codon (TAG) in the catalytic domain. This mutation abolished a FokI restriction site. The PCR product from normal subjects was digested with FokI and yielded two fragments, one of 223 bp and one of 47 bp. The PCR product from the patient gave a single 270-bp fragment, demonstrating possible homozygosity.

Aged↗
PubMed2000

Characterization of Ca(2+) channels in rat subthalamic nucleus neurons.

The subthalamic nucleus (STN) plays a key role in motor control. Although previous studies have suggested that Ca(2+) conductances may be involved in regulating the activity of STN neurons, Ca(2+) channels in this region have not yet been characterized. We have therefore investigated the subtypes and functional characteristics of Ca(2+) conductances in STN neurons, in both acutely isolated and slice preparations. Acutely isolated STN cells were identified by retrograde filling with the fluorescent dye, Fluoro-Gold. In acutely isolated STN neurons, Cd(2+)-sensitive, depolarization-activated Ba(2+) currents were observed in all cells studied. The current-voltage relationship and current kinetics were characteristic of high-voltage-activated Ca(2+) channels. The steady-state voltage-dependent activation curves and inactivation curves could both be fitted with a single Boltzmann function. Currents evoked with a prolonged pulse, however, inactivated with multiple time constants, suggesting either the presence of more than one Ca(2+) channel subtype or multiple inactivation processes with a single channel type in STN neurons. Experiments using organic Ca(2+) channel blockers revealed that on average, 21% of the current was nifedipine sensitive, 52% was sensitive to omega-conotoxin GVIA, 16% was blocked by a high concentration of omega-agatoxin IVA (200 nM), and the remainder of the current (9%) was resistant to the co-application of all blockers. These currents had similar voltage dependencies, but the nifedipine-sensitive current and the resistant current activated at slightly lower voltages. omega-Agatoxin IVA at 20 nM was ineffective in blocking the current. Together, the above results suggest that acutely isolated STN neurons have all subtypes of high-voltage-activated Ca(2+) channels except for P-type, but have no low-voltage-activated channels. Although acutely isolated neurons provide a good preparation for whole cell voltage-clamp study, dendritic processes are lost during dissociation. To gain information on Ca(2+) channels in dendrites, we thus studied Ca(2+) channels of STN neurons in a slice preparation, focusing on low-voltage-activated channels. In current-clamp recordings, a slow spike was always observed following termination of an injected hyperpolarizing current. The slow spike occurred at resting membrane potentials and was sensitive to micromolar concentrations of Ni(2+), suggesting that it is a low-threshold Ca(2+) spike. Together, our results suggest that STN neurons express low-voltage-activated Ca(2+) channels and several high-voltage-activated subtypes. Our results also suggest the possibility that the low-voltage-activated channels have a preferential distribution to the dendritic processes.

Action Potentials↗