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Biomedical subjects

T Mutoh

Publications and source records attributed to T Mutoh.

At least 73 records · Page 4Linked to original sources

Putative gap junctional communication between axon and regenerating Schwann cells during mammalian peripheral nerve regeneration.

Gap junctions are intercellular channels which mediate the traffic of ions and a variety of molecular messengers between contiguous cells. Here, we report on the possibility that atypical gap junctions develop between heterologous tissues, such as regenerating nerve axons and Schwann cells, during peripheral nerve regeneration in adult rats. After a complete transection and subsequent regeneration in the rat sciatic nerve distal segment, a small scale gap junction-like structure was observed between the regenerating axons and adjoining Schwann cells. Immunoelectron microscopy showed that one of the gap junctional proteins, connexin32, was located at a small region of contact between the axon and Schwann cells. Biocytin, a small molecular weight dye, was transported from regenerating axons into adjoining Schwann cells. The present findings suggest that regenerating axons communicate directly with adjacent Schwann cells through small gap junctions, which may play a role in the mechanism of regeneration following nerve transection.

Animals↗

[Coxsackie virus B4 encephalitis in a young female who developed mental symptoms, and consciousness disturbance, and completely recovered].

An 18-year-old female had common cold and insomnia in early March 1987. Later, abnormal speech and behavior, emotional incontinence, anorexia and consciousness disturbance appeared. On March 19, she was admitted to our hospital in semi-comatose state. Myoclonus-like movement on hands was observed, and epileptic attacks with tonic and clonic convulsions occasionally occurred. There were no neurological findings that suspected cerebral focal lesions. The respiration was assisted through tracheal intubation. Laboratory examinations showed inflammatory reactions (CRP+2, WBC 10,600) and transient high levels serum CK (6,215 IU). As she had bradycardia (30-40/min) with complete AV block on ECG, the pacemaker was implanted. The complication of myocarditis was suspected. EEG showed bilateral slow waves (3-6Hz), dominantly in frontal areas. Brain CT and CSF examinations were normal. After the combined administration of ara-A, dexamethasone and anti-convulsant, the consciousness level was recovered within a month. The serum antibody against coxsackie virus B4 alone was significantly increased. We concluded that coxsackie virus B4 caused acute encephalitis with mental symptoms and myocarditis with AV block. Recently, cytomegalovirus was reported to be the causative virus in a young female with non-HSV encephalitis who showed mental symptoms with good prognosis, but coxsackie virus B4 should also be considered as one of the causative viruses.

Adolescent↗

GM1 gangliosidosis type 3 with severe jaw-closing impairment.

The patient had adult GM1 gangliosidosis (type 3) with severe impairment of mastication caused by dystonia of anterior digastric muscles (jaw-opener) on clenching. This is the first report on jaw dystonia severe enough to cause the masticatory impairment in adult GM1 gangliosidosis. The discordance of closing and opening muscles during mastication might be caused by a basal ganglia lesion in this disease.

Adult↗

Chorea-acanthocytosis with polyclonal antibodies to ganglioside GM1.

A patient with chorea-acanthocytosis presenting with axonal neuropathy showed an elevation in IgM polyclonal antibodies to the GM1 ganglioside, which were estimated by enzyme-linked immunosorbent assay and complement-mediated liposome immune lysis assay (LILA). This is the first demonstration of such antibodies in chorea-acanthocytosis. Anti-GM1 antibodies might have directly caused the axonal neuropathy by binding to GM1 or cross-reactive antigens in the nerves.

Acanthocytes↗

Cardiovascular reflex mechanisms by topical instillation of capsaicin and distilled water into the larynx in anesthetized dogs.

Cardiovascular reflex mechanisms by topical laryngeal instillation of capsaicin (CAPS) or distilled water were evaluated in anesthetized chronic tracheostomized dogs. Both CAPS (10 micrograms/ml) and water instillation into the isolated upper airway caused a significant decrease in heart rate (P < 0.05) and a significant increase in blood pressure (P < 0.05) from the values before instillation under both spontaneous and controlled ventilation. The bradycardia was significantly reduced by atropine pretreatment (P < 0.05) and the hypertension was significantly decreased by phentolamine and propranolol pretreatments (P < 0.01). A higher concentration of CAPS (100 micrograms/ml) instillation considerably reduced the response to subsequent CAPS (100 micrograms/ml) instillation, whereas the response to water was sustained, indicating the desensitization of laryngeal CAPS-sensitive endings. All the reflex responses to CAPS and water were eliminated by topical anesthesia with lidocaine. It was concluded that the laryngeal cardiovascular reflex responses were mediated by the afferents such as the laryngeal CAPS-sensitive presumably C-fiber endings or water-responsive receptors and by both the parasympathetic and sympathetic nervous systems as efferents.

Administration, Topical↗

Cardiopulmonary effects of sevoflurane, compared with halothane, enflurane, and isoflurane, in dogs.

OBJECTIVE: To evaluate cardiopulmonary effects of sevoflurane (Sevo), compared with halothane (Hal), enflurane (Enf), and isoflurane (Iso). ANIMALS: 24 healthy Beagles, randomly assigned to 4 groups of 6 dogs each. PROCEDURE: Dogs under spontaneous ventilation were anesthetized with Sevo, Hal, Enf, or Iso. After minimum elveolar concentration (MAC) of each anesthetic was determined, anesthesia was maintained at light (1 MAC), moderate surgical (1.5 MAC), and deep (2 MAC), stages and cardiopulmonary variables at conscious state (baseline) and each anesthesia stage were measured. RESULTS: In dogs of the Sevo group, heart rate increased significantly from the baseline value at all anesthesia stages. Systemic vascular resistance during Sevo anesthesia decreased gradually with increasing anesthesia stage, which was accompanied by dose-dependent decreases in systolic, mean, and diastolic arterial blood pressures. At 1.5 and 2 MAC Sevo, stroke index decreased slightly but significantly from the baseline value; however, cardiac index was unchanged because of the significant increase in heart rate. Respiratory rate decreased significantly at 2 MAC from that at 1 MAC Sevo. Tidal volume and dead space-to-tidal volume ratio were unchanged at all anesthesia stages of Sevo, resulting in significantly decreased expired and alveolar ventilation at 2 MAC, compared with values at 1 and 1.5 MAC Sevo. PaCO2 increased and pHa decreased significantly, depending on anesthesia stage; PaO2, increased significantly from baseline values, and remained constant because of inhalation of 100% O2. CONCLUSION: Cardiovascular effects of Sevo were greater than those of Hal, similar to those of Iso, and less than those of Enf. Respiratory effects of Sevo were similar to those of Iso at all anesthesia stages, greater than those of Hal at 2 MAC, and less than those of Enf at 1.5 and 2 MAC. Up to the moderate surgical anesthesia stage, Sevo can be used safely in dogs undergoing spontaneous ventilation.

Anesthetics, Inhalation↗

Tight junctions between the axon and Schwann cell during PNS regeneration.

We report here that during PNS regeneration, short focal tight junctions are present at the interface of regenerating axons and Schwann cells in the distal part of the transected nerve. When regrowing axons were seen in the distal segment, focal fusions of axonal and Schwann cell membranes were observed on electron microscopy. Freeze-fracture study showed short arrays of intramembrane particles in the contacting membrane of axons and Schwann cells. Immunohistochemical study revealed the localization of ZO-1 tight junction associated protein at discrete sites of axon-Schwann cell contact. These results suggest that mechanical links of the axon and Schwann cell by means of short tight junctions are involved in axon-Schwann cell contact events during PNS regeneration.

Animals↗

Ganglioside GM1 binds to the Trk protein and regulates receptor function.

Several lines of evidence have suggested that ganglioside GM1 stimulates neuronal sprouting and enhances the action of nerve growth factor (NGF), but its precise mechanism is yet to be elucidated. We report here that GM1 directly and tightly associates with Trk, the high-affinity tyrosine kinase-type receptor for NGF, and strongly enhances neurite outgrowth and neurofilament expression in rat PC12 cells elicited by a low dose of NGF that alone is insufficient to induce neuronal differentiation. The potentiation of NGF activity by GM1 appears to involve tyrosine-autophosphorylation of Trk, which contains intrinsic tyrosine kinase activity that has been localized to the cytoplasmic domain. In the presence of GM1 in culture medium, there is a > 3-fold increase in NGF-induced autophosphorylation of Trk as compared with NGF alone. We also found that GM1 could directly enhance NGF-activated autophosphorylation of immunoprecipitated Trk in vitro. Monosialoganglioside GM1, but not polysialogangliosides, is tightly associated with immunoprecipitated Trk. Furthermore, such tight association of GM1 with Trk appears to be specific, since a similar association was not observed with other growth factor receptors, such as low-affinity NGF receptor (p75NGR) and epidermal growth factor receptor (EGFR). Thus, these results strongly suggest that GM1 functions as a specific endogenous activator of NGF receptor function, and these enhanced effects appear to be due, at least in part, to tight association of GM1 with Trk.

Animals↗

Indocyanine green fundus angiography of retrobulbar vasculature.

OBJECTIVE: To report the observations of the retrobulbar vasculature with indocyanine green angiography. METHODS: We performed fluorescein and indocyanine green angiography with a fundus camera (TRC501A) at a university medical center. We examined 12 patients (three men and nine women) with pathologic myopia. RESULTS: With these methods, retrobulbar vessels could be observed in the eyes of these patients with pathologic myopia and thin sclera. The location of the vessels could be changed by altering eye position. CONCLUSION: With fluorescein angiography, we were able to visualize some of the retrobulbar vasculature in selected areas, but indocyanine green angiography was apparently superior to fluorescein angiography.

Adult↗

Rapid inhalation induction of anesthesia by halothane, enflurane, isoflurane and sevoflurane and their cardiopulmonary effects in dogs.

The rapid inhalation induction of anesthesia (RII) by mask inhalation of halothane, enflurane, isoflurane and sevoflurane at an equianesthetic concentration (2.5 MAC) was evaluated in 24 beagle dogs. The differences in movements, induction and intubation time between anesthetics were mainly associated with the differences in each blood/gas solubility. The most rapid and smoothest induction was observed by sevoflurane inhalation (209.0 +/- 44.2 sec), followed by isoflurane inhalation (285.8 +/- 34.1 sec). Halothane inhalation took the longest induction time (790.3 +/- 75.7 sec). Movements during RII were minimal in sevoflurane group comparing to the other groups. Heart rate, cardiac output and rate pressure product significantly increased after the beginning of inhalation in all the dogs except for those of halothane group. These changes exceeded the physiological level just after the beginning of inhalation, however, rapidly reversed to the maintenance level (1.5 MAC) approximately 10 min after intubation. Consequently, sevoflurane seemed to be the best inhalational anesthetic for RII in dogs without significant problems in respiratory and/or cardiac functions. Isoflurane also induced rapid induction with some degree of the movements.

Analysis of Variance↗

Clinical application of rapid inhalation induction of anesthesia using isoflurane and sevoflurane with nitrous oxide in dogs.

Clinical usefulness of rapid inhalation induction of anesthesia (RII) using 5.0 vol.% isoflurane (GOI) and sevoflurane (GOS) with N2O was evaluated in 124 canine patients. Induction times, loss of various reflexes and movement times were significantly faster in GOI group than in GOS group. Scores for the easiness of intubation and the degree of movements were also significantly less in GOI group than in GOS group. Positive correlation between body weight and degree of movements was observed in both induction groups. Thus, RII using GOI is a practically useful and safe induction modality in small- to medium-sized dogs.

Age Factors↗

[Detection of hepatitis B virus by using polymerase chain reaction and nonradioactive DNA probes. I. Identification of mutations in the precore region by PCR-direct sequencing and ASO probe method].

Seroconversion from hepatitis B e antigen (HBeAg) to anti-HBe antibody (anti-HBe) frequently occurs in hosts chronically infected with hepatitis B virus (HBV). Further, this phenomenon is related to a point mutation from guanine to adenine at nucleotide 83 in the precore region of HBV, which, converts codon 28 for tryptophan (TGG:W) to a translational, stop codon (TAG:X). Therefore, we decided to examine HBV in sera from patients for mutations in the precore region by a simple allele-specific oligonucleotide (ASO) probe method. Direct sequencing was first performed on DNA fragments amplified by the polymerase chain reaction in order to establish whether there were mutations in the precore region. Subsequently, specific DNA probes were applied to detection of mutations in the precore region. Subsequently, specific DNA probes were applied to detection of mutations in the precore gene. Five unknown mutations (I10N, C12W, C14S, V17F and A19D), three known mutations (I9V, W28X and G29D) and for novel nucleotide insertions were identified in anti-HBe positive sera. By using seven nonradioactive probes, we could determine the mutations at codons 9, 28 and 29 in anti-HBe positive sera. The W28X mutation was found in anti-HBe positive but not in any of HBeAg positive sera. Meanwhile, wild-type strains of HBV were detectable in sera from patients who were positive to HBeAg or anti-HBe. This ASO probe assay could determine in a few days the mutations in the precore region of HBV, especially including the defect to prohibit the synthesis and secretion of HBeAg.

Amino Acid Sequence↗

[Screening methods for the diagnosis of lysosomal storage disease].

Lysosomal storage disease is one of the inborn errors of metabolism caused by a deficiency of lysosomal acid hydrolase activity. We describe here the details of screening methods for the diagnosis of this disorder. It is definitely important to perform both enzyme assay of acid hydrolases and the detection of accumulated materials in patient's tissues. Leukocytes (lymphocytes), serum or plasma, and cultured skin fibroblasts are commonly used as the enzyme source for the assay. Although most lysosomal storage diseases can be diagnosed using leukocytes as the enzyme source, enzymatic activities of beta-glucosidase and sialidase in leukocytes are sometimes normal even in patients. At present, the most reliable enzyme source is considered to be cultured skin fibroblasts. Nevertheless, we should remind that we cannot detect a deficiency of galactocerebroside beta-galactosidase activity even using fibroblasts, if we use synthetic substrate. Natural substrates should be employed for the correct diagnosis and for the study of the nature of patient's enzyme. Deficiency of the enzymatic activity in patients should be confirmed by the demonstration of accumulated materials due to the enzyme defect in patient's tissues and urine. The accumulation of mucopolysaccharides and oligosaccharides in urine is obvious in patients with mucopolysaccharidoses and mucolipidoses, respectively. In case of sphingolipidoses, rectal biopsy specimen and blood could be a target of the investigation. In final, the choice of these screening methods should be made solely based on the detailed clinical manifestation of patients.

Glycosaminoglycans↗

Survey of complications of indocyanine green angiography in Japan.

PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.

Aged↗

1-Methyl-4-phenylpyridinum kills differentiated PC12 cells with a concomitant change in protein phosphorylation.

1-Methyl-4-phenylpyridinum (MPP+), a selective neurotoxin, destroys the dopaminergic nigrostriatal pathway and results in a parkinsonian syndrome. Exposure of differentiated PC12 cells with nerve growth factor for 5 days to MPP+ (100 microM) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP+ treatment (100 microM) concomitantly stimulates S6 kinase activity and resultant phosphorylation of S6 protein of 40S ribosomal subunits in the cells. Cycloheximide treatment prevents the MPP(+)-induced DNA fragmentation and enhancement of the phosphorylation of S6 protein. The present data demonstrate that neurotoxin, MPP+, kills differentiated PC12 cells by the apparent involvement of apoptotic process. Furthermore, the data strongly suggest that a change in protein phosphorylation might be involved in the signal transduction of MPP+ neurotoxicity and/or the protection from its toxicity.

1-Methyl-4-phenylpyridinium↗

Abundant but inactive-state gp140proto-trk is expressed in neuroblastomas of patients with good prognosis.

Steady-state levels of gp140proto-trk in cell lines and tumor tissues of neuroblastoma were examined by immunoblotting with anti-gp140proto-trk. The level of gp140proto-trk varied but showed good correlations with the stage of the tumor and the age of the patients at the time of diagnosis. Moreover, patients with higher expression of gp140proto-trk clearly had a far better survival rate than those with lower expression, suggesting that suppression of gp140proto-trk strongly correlates with the malignant conversion of the tumor. However, we found that neither autophosphorylation of gp140proto-trk nor tyrosine phosphorylation of cellular proteins was elevated in tumors of the higher expression group. These results suggest that gp140proto-trk does not actively participate in the process of transformation or the suppression of malignant conversion. Rather, the higher level of gp140proto-trk may reflect the greater level of differentiation of tumor cells.

Age Factors↗