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Biomedical subjects

M Nagamatsu

Publications and source records attributed to M Nagamatsu.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nerve growth factor maintains regulation of intracellular calcium in neonatal sympathetic neurons but not in mature or aged neurons.

We examined the effects of nerve growth factor on the regulation of intracellular calcium levels of superior cervical ganglion neurons in terms of postnatal maturation and ageing. Rat superior cervical ganglion neurons from three age groups (neonatal: 0 to one-day-old, young adult: three to six-month-old, and aged: more than 24-month-old) were dissociated and cultured in the presence or absence of 100 ng/ml of nerve growth factor. Intracellular free calcium levels ([Ca2+]i) were measured using the fura-2 microfluorometry. Nerve growth factor treatment increased the resting [Ca2+]i of neonatal neurons, although it had no effect on those of mature and aged neurons. We further examined the effects of nerve growth factor on the transient increase of [Ca2+]i induced by methacholine (0.1 mM), caffeine (20 mM) or high-potassium medium (40 mM K+). Nerve growth factor pre-treatment significantly increased the population of neonatal superior cervical ganglion neurons which responded to methacholine, whereas almost all young adult and aged neurons responded to methacholine regardless of pre-treatment of nerve growth factor. Caffeine induced a cyclic alteration of [Ca2+]i (oscillation) in 45% of the neonatal superior cervical ganglion neurons when they were maintained without nerve growth factor, but nerve growth factor treatment suppressed the oscillation to 10% of neurons. In contrast to neonatal neurons, all of the young adult and aged neurons showed only a transient increase of [Ca2+]i in response to caffeine independent of nerve growth factor treatment. There was no significant effect of nerve growth factor on K+ depolarization-induced [Ca2+]i elevations at any of the ages studied. Nerve growth factor did not substantially alter the pattern of the transients induced by these three agents. Our results indicate that exogenous nerve growth factor is necessary to maintain normal acetylcholine receptor-mediated [Ca2+]i responses as well as Ca(2+)-induced Ca2+ release from intracellular calcium storage in neonatal superior cervical ganglion neurons. In mature superior cervical ganglion neurons, Ca2+ homeostasis becomes independent of exogenous nerve growth factor, and Ca2+ homeostasis and its independency are well preserved in aged neurons.

Aging↗
PubMed1998

Somatic mosaicism of the expanded CAG trinucleotide repeat in mRNAs for the responsible gene of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA).

The CAG trinucleotide repeats in mRNAs for the responsible genes of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and X-linked spinal and bulbal muscular atrophy (SBMA) were examined in various neural and nonneural tissues of affected individuals. The tissue-specific variation of expanded CAG repeat alleles were apparent for mRNAs of all three genes. The expanded CAG repeats of the mRNA were shorter in the cerebellum than in other regions of the central nervous system in DRPLA and MJD, but not in SBMA, and were longer in the liver and colon in MJD. Transcripts of the responsible genes with expanded CAG repeats were detected in all tissues studied, and the tissue-specific variation in the CAG repeat size of the mRNA did not correlate with the tissue-specific severity of pathological involvement in these diseases.

Adult↗
PubMed1998

[Double filtration plasmapheresis (DFPP) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)].

We studied the therapeutic characteristics of double filtration plasmapheresis (DFPP) in 14 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The patients were classified into 2 subgroups of the responders (7 patients) and the non-responders (7 patients) to DFPP. The responders to DFPP were designated as those showing the improvement 2 or more grades in measures the activity of daily living by the modified Rankin scale (MRS). All these patients underwent neurological assessment, CSF study, electrophysiological studies at the beginning and end of treatment. Sural nerve biopsy study was performed in 10 cases. Neurological function was assessed serially using a quantitative neurological disability score (NDS). At the beginning of treatment, there were no significant differences in various measurements between the responders and the non-responders except for the frequency of demyelination. In responders, significant improvement was found in mean changes in MRS, NDS, motor nerve conduction velocity, compound muscle action potential, distal motor latency, while in non-responders, all measures remained unchanged or worsened. Muscle wasting was seen in 3/7 responders and 4/7 non-responders, and denervation potentials in needle EMG were seen in 1/7 responders and 3/7 non-responders. Four patients of the responders were classified as chronic relapsing course, and 6 patients of the non-responders as chronic progressive course. We conclude that DFPP was useful for the subgroups of CIDP patients, but the underlying immuno-pathological background that determine the efficacy of plasmapheresis should be elucidated.

Activities of Daily Living↗
PubMed1997

Acidity is involved in the development of neuropathy caused by oxidized cellulose.

Recently we demonstrated that oxidized cellulose (OC), a surgical topical hemostatic agent, induces subjacent nerve fiber degeneration by a diffusible chemical mechanism. Since OC is highly acidic, we examined the role of acidity in the development of neuropathy by OC in this study. Fifteen minutes' exposure to culture media containing OC (2 mg/ml, pH 3.47 or 10 mg/ml, pH 2.57) suppressed the subsequent neurite outgrowth of precultured rat DRG neurons in vitro. However, the neurotoxicity of OC disappeared when the pH of the media was restored to 7.42. Topical application of 20 mg OC lowered the pH in the subperineurium of the adjacent rat sciatic nerve to around 3, and kept it below 4 for 2 h in vivo. Application of 0.1 ml neutralized physiological saline containing 40 mg OC did not produce pathological changes in the adjacent rat sciatic nerve in vivo, in contrast to the marked subperineurial nerve damage by direct application of 20 or 40 mg OC observed in our previous study. These results strongly indicate that local neurotoxicity of OC is due to its high acidity. Further care is needed to avoid direct application of large amounts of OC to peripheral nerve.

Acids↗
PubMed1997

Skin sympathetic nerve activity in Guillain-Barré syndrome: a microneurographic study.

To assess autonomic dysfunction, skin sympathetic nerve activity (SSNA) of four patients with Guillain-Barré syndrome was microneurographically studied in the acute and remission phase. Autonomic symptoms such as sinus tachycardia, palmar hyperhidrosis, hypertension, and orthostatic hypotension were present in the acute phase, but all subsided during remission. Basal resting SSNA and the responses to various physical and mental stimuli were all increased in the acute phase and returned almost to normal during remission. Rate of response in sweat rate and blood flow against SSNA were kept proportionally constant during both the acute and remission phases. These findings suggest that some autonomic nerve symptoms of Guillain-Barré syndrome, particularly during the acute phase, are due to increased SSNA.

Acute Disease↗
PubMed1997

Sensory conduction study of cisplatin neuropathy: preservation of small myelinated fibers.

We report a patient with peripheral neuropathy caused by cisplatin for the treatment of testicular tumor. Routine studies of nerve conduction and somatosensory evoked potentials demonstrated large myelinated fiber neuropathy suggesting ganglioneuronopathy. We also performed a CO2 laser evoked potential study, and found that small myelinated fibers, which are related to pain sensation, were well preserved in this patient.

Adult↗
PubMed1996

Ischemic reperfusion causes lipid peroxidation and fiber degeneration.

Although the neuropathology of ischemic fiber degeneration (IFD) is relatively well known, its pathogenesis is poorly understood. One putative mechanism of IFD is oxidative stress, causing a breakdown of the blood-nerve barrier (BNB) and lipid peroxidation. We evaluated the effect of ischemic reperfusion of rat sciatic-tibial nerve seeking biochemical and pathologic evidence of BNB disruption and lipid peroxidation. Ischemia, caused by the ligation of the supplying arteries to sciatic-tibial nerve, was maintained for 3 h, followed by reperfusion. Reperfusion resulted in an increase in nerve lipid hydroperoxides, greatest at 3 h, followed by a gradual decline over the next month. Nerve edema and IFD consistently became more severe with reperfusion, indicating that oxidative stress impairs the BNB (edema) and causes IFD. Reduced reperfusion was greatest over distal sciatic nerve and midtibial nerve at day 7. The most ischemic segment (midtibial), of nonreperfused ischemic nerves (duration 3 h), underwent both edema and IFD that was as pronounced as those of other segments after reperfusion, and underwent a smaller increase with reperfusion, suggesting that ischemia alone can also cause IFD and edema. The type of fiber degeneration was that of axonal degeneration.

Animals↗
PubMed1995

Oxidized cellulose causes focal neuropathy, possibly by a diffusible chemical mechanism.

We observed incidentally that rat sciatic nerve in contact with oxidized cellulose (OC), an absorbable hemostatic agent, underwent focal fiber degeneration, and we undertook studies to determine the mechanism of its production. Topically applied OC generated acute nerve damage within the adjacent nerve fascicle of rat sciatic nerve in a dose-dependent fashion (r = 0.99, P < 0.01, threshold amount: 9.9 mg). IN single teased fibers, the predominant type of myelinated fiber damage was axonal degeneration. The subperineurial blood flow of the rat sciatic nerve was serially measured by microelectrode hydrogen polarography, and the reduction at 90 min after application of OC was not greater than that of controls. A thin polyethylene membrane interposed between OC and the sciatic nerve almost completely prevented the nerve damage. These data suggest that the chief mechanism of nerve damage by OC was neither compression nor ischemia, but was a diffusible chemical mechanism. Care should be taken to avoid direct OC application around peripheral nerves.

Animals↗
PubMed1995

Cerebrospinal fluid levels of S-100b protein and neuron-specific enolase in chronic inflammatory demyelinating polyneuropathy.

We measured the cerebrospinal fluid (CSF) concentrations of S-100b protein (S-100b) and neuron-specific enolase (NSE) using enzyme immunoassay methods in 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), other three patients with chronic neuropathy with demyelination, eight patients with various axonal neuropathies (AN), and 46 controls, to investigate the clinical usefulness of the determination of these two specific proteins in these neuropathies. S-100b levels were elevated (> the mean +/- 2 SD levels of controls) in the majority of patients with clinically progressing CIDP (9/11), but not in the patients with AN (0/8). In parallel with the clinical improvement, S-100b levels were normalized in patients with CIDP (10/10), though total protein levels in the CSF still remained high in some of these patients (5/10). Elevation of NSE levels were seldom seen in clinically worsening patients with CIDP (1/11) or AN (1/8). Thus our results indicated that the level of S-100b in the CSF may be useful to assess the activity of actual disease process in CIDP.

Adolescent↗
PubMed1995

Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy.

OBJECTIVE: To determine whether lipoic acid (LA) will reduce oxidative stress in diabetic peripheral nerves and improve neuropathy. RESEARCH DESIGN AND METHODS: We used the model of streptozotocin-induced diabetic neuropathy (SDN) and evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF), electrophysiology, and indexes of oxidative stress in peripheral nerves affected by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA, in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times per week after onset of diabetes. RESULTS: NBF in SDN was reduced by 50%; LA did not affect the NBF of normal nerves but improved that of SDN in a dose-dependent manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited normal NBF. The most sensitive and reliable indicator of oxidative stress was reduction in reduced glutathione, which was significantly reduced in streptozotocin-induced diabetic and alpha-tocopherol-deficient nerves; it was improved in a dose-dependent manner in LA-supplemented rats. The conduction velocity of the digital nerve was reduced in SDN and was significantly improved by LA. CONCLUSIONS: These studies suggest that LA improves SDN, in significant part by reducing the effects of oxidative stress. The drug may have potential in the treatment of human diabetic neuropathy.

Animals↗
PubMed1994

Molecular cloning of a novel protein-tyrosine phosphatase containing a membrane-binding domain and GLGF repeats.

A full-length cDNA encoding a novel cytosolic protein-tyrosine phosphatase (PTP), PTP-BAS, was cloned from human basophils. Due to in-frame deletions in the coding region, PTP-BAS exists in three isoforms: 7,455 bp (2,485 aa) for type 1, 7,398 bp (2,466 aa) for type 2 and 6,882 bp (2,294 aa) for type 3. All three isoforms contain a single PTP catalytic domain at the carboxyl termini as well as two distinct structural sequences. Amino terminal sequences of 300 amino acids are homologous to membrane-binding domains of cytoskeleton-associated proteins. Three 90 amino acid internal repetitive sequences are homologous to the GLGF repeats found in guanylate kinase proteins. PTP-BAS was expressed in various human tissues, especially highly in the kidney and lung. Interestingly, the BAS mRNA level in the fetal brain was remarkably high.

Adult↗
PubMed1993

Morphometric analysis of the sural nerve in experimental dorsal rhizotomy in rats.

To investigate the histological changes in the sural nerve by the damage to the centrally projected axon (CPA), we examined light-microscopic findings after dorsal rhizotomy. The L4-6 dorsal roots were cut unilaterally near the entry zone, with minimal laminectomy, in 27 anesthetized 8- to 10-week-old Sprague-Dawley rats. Animals were killed 1, 2, 4 and 8 weeks and 6 months after surgery, and morphometric results from the sural nerves on the side of the rhizotomy were compared with those from the unaffected side. There were no significant differences in total number, density, frequency distribution of diameters, thickness of myelin, and axonal circularity of myelinated fibers. In an analysis of teased fibers, neither demyelinated nor remyelinated fibers were found, and significant axonal degeneration was found in only 1 of 27 sural nerves on the side of the rhizotomy. These results suggest that pathological damage to the sural nerve is not the product of CPA lesions, even if the subject has dorsal root lesions at some distance from the ganglion.

Animals↗
PubMed1993

[Pharmacokinetic study on aspoxicillin transfer into pulmonary and tracheal tissues].

Each of 36 patients who underwent tracheotomy for removal of malignant or benign tumors or for treatment of pneumothorax was infused with 2 g of aspoxicillin (ASPC, Doyle injection) intravenously over 1-hour period. ASPC concentrations determined at 1 postoperative time-point in tissues of the lung and trachea and in serum of each patient were analyzed pharmacokinetically to elucidate the transfer of ASPC to the thoracic tissues. The preventive effect of ASPC against postoperative infections was also investigated in 39 tracheotomy patients. 1. The analysis of ASPC concentrations in 36 patients with tracheotomy gave the following results; 1) The peak blood level (about 80 micrograms/ml) was attained at the end of infusion. The serum level then decreased with time to below about 10 micrograms/ml at 6 hours after the start of infusion, with an elimination half-life of about 1.4 hours, which was comparable to that in healthy adults. 2) Peak levels in the lung and tracheal tissues were achieved at about 30 minutes after the start of infusion, at levels of about 30 and 40 micrograms/g, respectively, which decreased to about 5 micrograms/g in both tissues at 6 hours after the start of infusion. 2. Thirty nine patients who were treated with ASPC before operation were examined for the preventive effect of ASPC against postoperative infections for 1 week after operation. No postoperative infection was noted in any patients and ASPC was found to be useful for prevention of postoperative infections. 3. No side effects or abnormal laboratory findings were noted in any patients. Based on the results of the transfer into the tissues of respiratory organs and preventive effect against postoperative infections, we have concluded that ASPC is useful for prevention of infections after thoracic operation.

Adolescent↗
PubMed1992

Serial histologic investigation of squamous epithelial dysplasia associated with carcinoma of the esophagus.

Esophageal dysplasia and carcinoma were reviewed in the surgical specimens obtained from 37 patients with squamous cell carcinoma and 4 with adenocarcinoma; special attention was paid to the continuity of both lesions. Two hundred forty dysplasias and 113 carcinomas in situ (CIS) were recognized in the squamous cell carcinoma cases and 2 dysplasias and no CIS in the adenocarcinoma cases. The CIS often was accompanied continuously by severe dysplasia rather than mild or moderate dysplasia, suggesting some relationship between the CIS and the severity of dysplasia. However, many dysplastic lesions were located separately from the carcinoma. The frequency of appearance of the dysplasia near the CIS was low (11%), demonstrating a negative dysplasia-CIS sequence in many of the esophageal cancers. Lymphocytic infiltration was investigated further beneath the dysplasia or CIS. The degree of lymphocytic infiltration with lymphoid follicles correlated with the severity of dysplasia and was the highest in CIS.

Adenocarcinoma↗
PubMed1992

Enhanced production of interleukin 1 and tumor necrosis factor by peripheral monocytes after lentinan administration in patients with gastric carcinoma.

The effect of intravenous administration of lentinan, an immunopotentiating polysaccharide, on the production of interleukin 1-alpha (IL 1-alpha), interleukin 1-beta (IL 1-beta) and tumor necrosis factor-alpha (TNF-alpha) by monocytes in peripheral blood mononuclear cells (PBM) was studied in patients with gastric carcinoma. Peripheral blood samples were obtained from 10 patients before and 3, 5 and 7 days after a single dose of 2 mg lentinan injection. The ability of monocytes in PBM to produce IL 1-alpha was significantly augmented 3 and 5 days after lentinan administration, as compared with that before treatment. IL 1-beta production was also significantly increased 3, 5 and 7 days after the drug injection. Further, the capacity to produce TNF-alpha was significantly enhanced 3, 5 and 7 days after the drug administration. Thus, it is likely that the augmentation of these cytokine's production may contribute to the antitumor action of lentinan in patients with gastric carcinoma.

Humans↗
PubMed1992

Enhanced induction of lymphokine-activated killer activity after lentinan administration in patients with gastric carcinoma.

In 15 patients with gastric carcinoma, peripheral blood mononuclear cells (PBM) were obtained serially before and 3, 5 and 7 days after lentinan administration. The generation of lymphokine-activated killer (LAK) activity, induced by in vitro activation of PBM with interleukin 2 (IL 2), was significantly augmented 5 days after a single intravenous dose of 2 mg lentinan, when compared with that before lentinan injection. Natural killer (NK) activity of PBM was also significantly enhanced 7 days after the drug injection. However, the distribution of lymphocyte subsets exhibited no significant change following lentinan administration.

Cell Separation↗