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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 199 records · Page 11Linked to original sources
PubMed1998

Bisecting GlcNAc structure is implicated in suppression of stroma-dependent haemopoiesis in transgenic mice expressing N-acetylglucosaminyltransferase III.

Several sugar structures have been reported to be necessary for haemopoiesis. We analysed the haematological phenotypes of transgenic mice expressing beta-1,4 N-acetylglucosaminyltransferase III (GnT-III), which forms bisecting N-acetylglucosamine on asparagine-linked oligosaccharides. In the transgenic mice, the GnT-III activity was elevated in bone marrow, spleen and peripheral blood and in isolated mononuclear cells from these tissues, whereas no activity was found in these tissues of wild-type mice. Stromal cells after long-term cultures of transgenic-derived bone marrow and spleen cells also showed elevated GnT-III activity, compared with an undetectable activity in wild-type stromal cells. As judged by HPLC analysis, lectin blotting and lectin cytotoxicity assay, bisecting GlcNAc residues were increased on both blood cells and stromal cells from bone marrow and spleen in transgenic mice. The transgenic mice displayed spleen atrophy, hypocellular bone marrow and pancytopenia. Bone marrow cells and spleen cells from transgenic mice produced fewer haemopoietic colonies. After lethal irradiation followed by bone marrow transplantation, transgenic recipient mice showed pancytopenia compared with wild-type recipient mice. Bone marrow cells from transgenic donors gave haematological reconstitution at the same level as wild-type donor cells. In addition, non-adherent cell production was decreased in long-term bone marrow cell cultures of transgenic mice. Collectively these results indicate that the stroma-supported haemopoiesis is compromised in transgenic mice expressing GnT-III, providing the first demonstration that the N-glycans have some significant roles in stroma-dependent haemopoiesis.

Acetylglucosamine↗
PubMed1998

Alterations with aging and ischemia in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in postmortem human putamen. Implications for susceptibility to parkinsonism.

Nicotine activates the dopaminergic system and acts to alleviate hypokinetic disorders (parkinsonism). The frequency of parkinsonism increases with age and is sometimes associated with multiple small infarcts (status lacunaris) in the putamen. To investigate changes with aging in control cases free from neurological disease and changes in cases with multiple small infarcts (status lacunaris) in the putamen, the present study determined nicotinic acetylcholine receptor (nAChR) subunit alpha4 and beta2 messenger RNA (mRNA) expression in the postmortem human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). In controls, alpha4 subunit mRNA expression was unaltered, but beta2 subunit mRNA expression decreased significantly with age. In cases with status lacunaris, both beta2 and alpha4 subunit mRNA expressions were significantly lower than in the control cases. The reduction in beta2 mRNA expression alone, or in both alpha4 and beta2 mRNA expressions, suggests a reduction in functional nAChRs in the putamen, which may in part explain the susceptibility to hypokinetic disorders of the elderly and subjects with ischemic damage in the striatum.

Adult↗
PubMed1998

Age-related changes in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in postmortem human frontal cortex and hippocampus.

Age-related changes in nicotinic acetylcholine receptor (nAChR) subunit alpha4 and beta2 messenger RNA (mRNA) expression in the postmortem human frontal cortex and hippocampus was investigated using the reverse transcription-polymerase chain reaction (RT-PCR). In the frontal cortex, both alpha4 and beta2 subunit mRNA expression decreased with age. In the hippocampus, alpha4 subunit mRNA expression was unaltered, while beta2 subunit mRNA expression significantly decreased with age. These findings suggest that nAChR transcription decreases during aging with differing vulnerability between subunits and brain regions, which could in part contribute to the reduction in cognitive functions seen in the elderly.

Adult↗
PubMed1998

Muscarinic facilitation of GABA release in substantia gelatinosa of the rat spinal dorsal horn.

1. Blind patch clamp recordings were made from substantia gelatinosa (SG) neurones in the adult rat spinal cord slice to study the mechanisms of cholinergic modulation of GABAergic inhibition. 2. In the majority of SG neurones tested, carbachol (10 microM) increased the frequency (677 % of control) of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs). A portion of these events appeared to result from the generation of spikes by GABAergic interneurones, since large amplitude IPSCs were eliminated by tetrodotoxin (1 microM). 3. The effect of carbachol on spontaneous IPSCs was mimicked by neostigmine, suggesting that GABAergic interneurones are under tonic regulation by cholinergic systems. 4. The frequency of GABAergic miniature IPSCs in the presence of tetrodotoxin (1 microM) was also increased by carbachol without affecting amplitude distribution, indicating that acetylcholine facilitates quantal release of GABA through presynaptic mechanisms. 5. Neither the M1 receptor agonist McN-A-343 (10-300 microM) nor the M2 receptor agonist, arecaidine (10-100 microM), mimicked the effects of carbachol. All effects of carbachol and neostigmine were antagonized by atropine (1 muM), while pirenzepine (100 nM), methoctramine (1 microM) and hexahydrosiladifenidol hydrochloride, p-fluoro-analog (100 nM) had no effect. 6. Focal stimulation of deep dorsal horn, but not dorsolateral funiculus, evoked a similar increase in IPSC frequency to that evoked by carbachol and neostigmine. The stimulation-induced facilitation of GABAergic transmission lasted for 2-3 min post stimulation, and the effect was antagonized by atropine (100 nM). 7. Our observations suggest that GABAergic interneurones possess muscarinic receptors on both axon terminals and somatodendritic sites, that the activation of these receptors increases the excitability of inhibitory interneurones and enhances GABA release in SG and that the GABAergic inhibitory system is further controlled by cholinergic neurones located in the deep dorsal horn. Those effects may be responsible for the antinociceptive action produced by the intrathecal administration of muscarinic agonists and acetylcholinesterase inhibitors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1998

Immunological assessment of the distribution of type VII adenylyl cyclase in brain.

The localization of the nine identified isoforms of adenylyl cyclase in brain has been largely based on determination of patterns of mRNA expression. A polyclonal antibody has now been developed that specifically recognizes Type VII adenylyl cyclase. This antibody was used for immunocytochemical analysis of the distribution of Type VII adenylyl cyclase in rat brain. Labeling of Type VII adenylyl cyclase was observed in several areas, including cerebellum, caudate-putamen, nucleus accumbens, hippocampus and cerebral cortex. In some of these areas, the staining of the adenylyl cyclase protein suggested the possibility of presynaptic localization. For example, in situ hybridization showed Type VII adenylyl cyclase mRNA concentrated in cerebellar granule neurons. The cerebellar granule cell layer, however, showed little immunostaining, while punctate immunostaining was observed in the molecular layer. These results suggested that protein synthesized in the granule neurons may be targeted to the neuron terminals. Punctate staining in the caudate-putamen, globus pallidus and nucleus accumbens also suggested the possibility of axonal and/or dendritic localization of Type VII adenylyl cyclase in these regions. Labeling of the soma of cerebellar Purkinje cells, cortical pyramidal and non-pyramidal cells and interneurons in the cerebellum and hippocampus was also observed. Type VII adenylyl cyclase, like the other adenylyl cyclase isoforms, has distinct regulatory characteristics, including sensitivity to stimulation by Gsalpha and G protein betagamma subunits, modulation by protein kinase C, and high sensitivity to stimulation by ethanol. These characteristics, and the discrete localization of this enzyme, may contribute to its ability to provide signal integration and/or control of neurotransmitter release in particular neurons or brain areas.

Adenylyl Cyclases↗
PubMed1998

Ectopic expression of N-acetylglucosaminyltransferase III in transgenic hepatocytes disrupts apolipoprotein B secretion and induces aberrant cellular morphology with lipid storage.

N-Acetylglucosaminyltransferase III (GnT-III) produces "bisecting-GlcNAc" and regulates the branching of N-glycans. GnT-III activity is elevated during hepatocarcinogenesis, which is in contrast to the undetectable level found in normal hepatocytes. To determine the biological significance of GnT-III in hepatocytes, transgenic mice that specifically express GnT-III in the liver were established and characterized. The transgenic hepatocytes had a swollen oval-like morphology, with many lipid droplets. Apolipoprotein B, which contained increased level of bisecting-GlcNAc accumulated in the transgenic hepatocytes. In the transgenic serum, triglycerides, the beta- and pre-beta-lipoprotein fractions, and apolipoprotein B100 were significantly decreased, compared with levels in nontransgenic serum. These abnormal phenotypes were more prominent in the mice with more copies of the transgene and a resulting high GnT-III activity. We demonstrate that aberrant glycosylation, as the direct result of the formation of bisecting-GlcNAc, disrupts the function of apolipoprotein B, leading to the generation of fatty liver. This observation suggests a novel mechanism for the pathogenesis of fatty liver.

Animals↗
PubMed1998

Age-related changes in D1 and D2 receptor mRNA expression in postmortem human putamen with and without multiple small infarcts.

Expression of messenger RNAs (mRNAs) encoding the D1 and D2 dopamine receptors as a function of age was determined in the human putamen using the reverse transcription-polymerase chain reaction (RT-PCR). In cases without multiple small infarcts (status lacunaris) in the putamen, D1 mRNA expression was unaltered, while D2 mRNA expression significantly decreased with age. Both D1 and D2 mRNA expression was lower in cases with status lacunaris. The reduction in D1 receptors primarily located on striatonigral neurons or D2 receptors primarily located on striatopallidal neurons may inhibit thalamocortical neurons. The decreased transcription of D1 and D2 receptor genes may in part account for increased susceptibility to hypokinetic disorders in the elderly.

Actins↗
PubMed1998

Transsynaptic cell death of neurons following striatopallidal lesions does not occur in substantia nigra pars reticulata in developing rats

In adult rats, combined lesions of the striatum and globus pallidus (GP) cause transsynaptic cell death of neurons in the substantia nigra pars reticulata (SNr) which becomes apparent 1-2 weeks after the lesions. This delayed cell death of SNr neurons has been explained to be caused by over-excitation of SNr neurons which results from an imbalance between excitatory and inhibitory inputs due to two simultaneous events: acceleration of the excitatory input from the disinhibited subthalamic nucleus (STN) and deprivation of the inhibitory input from the striatum. To examine whether the transsynaptic neuronal death in SNr is caused by the same lesions in developing rats, we destroyed the striatum and GP in rats on postnatal days 10 (P10), P15, P20, P25, P30, P35 and P60 by injecting ibotenic acid. We found that cell death did not occur in SNr neurons in rats younger than P20 and that Fos expression induced in STN neurons after these striatopallidal lesions in P10 and P20 rats was lower than that in P30 or P60 rats. These findings suggest that excitation of STN neurons is not enough to cause cell death of SNr neurons in rats younger than P20. Immature functional connection between the cerebral cortex and STN in the early developing animals may contribute to the resistivity of SNr neurons to transsynaptic delayed cell death.

Journal Article↗
PubMed1998

Transsynaptic cell death of neurons following striatopallidal lesions does not occur in substantia nigra pars reticulata in developing rats.

In adult rats, combined lesions of the striatum and globus pallidus (GP) cause transsynaptic cell death of neurons in the substantia nigra pars reticulata (SNr) which becomes apparent 1-2 weeks after the lesions. This delayed cell death of SNr neurons has been explained to be caused by over-excitation of SNr neurons which results from an imbalance between excitatory and inhibitory inputs due to two simultaneous events: acceleration of the excitatory input from the disinhibited subthalamic nucleus (STN) and deprivation of the inhibitory input from the striatum. To examine whether the transsynaptic neuronal death in SNr is caused by the same lesions in developing rats, we destroyed the striatum and GP in rats on postnatal days 10 (P10), P15, P20, P25, P30, P35 and P60 by injecting ibotenic acid. We found that cell death did not occur in SNr neurons in rats younger than P20 and that Fos expression induced in STN neurons after these striatopallidal lesions in P10 and P20 rats was lower than that in P30 or P60 rats. These findings suggest that excitation of STN neurons is not enough to cause cell death of SNr neurons in rats younger than P20. Immature functional connection between the cerebral cortex and STN in the early developing animals may contribute to the resistivity of SNr neurons to transsynaptic delayed cell death.

Animals↗
PubMed1998

Long-term follow-up of the vascularized iliac bone graft.

We retrospectively studied four patients who were treated with vascularized iliac bone graft for reconstruction of the tibia. The average length of the graft was 9.8 cm. The follow-up period was 11-18 years (average, 14.8 years). Although two of them were osteomyelitis, no recurrence occurred. We also studied four patients who were treated with nonvascularized iliac bone graft for anterior spinal interbody fusion (average, 10.8 years). Cosmetic problem slightly exists because the vascularized iliac bone still showed the original shape, which was prominent from the tibial contour. The vascularized iliac bone marrow showed iso intensity in both T1 and T2 image of the MRI. However, nonvascularized iliac bone graft on the spine showed high intensity in both T1 and T2 imaging. Since the vascularized iliac bone graft does not present fatty degeneration, it shows strong resistance against infection.

Adult↗
PubMed1998

Two cases of synchronous multiple thymoma.

We report two cases of synchronous double primary thymoma without myasthenia gravis. These cases suggest the possibility of multicentric thymoma and confirm the validity of a complete thymectomy.

Adult↗
PubMed1998

Analysis of lobectomy for small peripheral lung cancer supports extended segmentectomy.

We reviewed the records of 53 patients who underwent lobectomy for peripheral non-small cell lung cancer under 2 cm in diameter and established a rationale for segmentectomy with intraoperative lymph nodes dissection (extended segmentectomy). Five patients (9.4%) had intrapulmonary metastases. Nodal status was N0 in 34 patients (64.2%), N1 in 7 (13.2%), and N2 in 12 (22.6%). Based on examination of intraoperative frozen sections, 31 patients lacking lymph node metastases and visceral pleural involvement could have been candidates for extended segmentectomy. Twenty-seven had stage I disease on postoperative examination of paraffin-embedded sections. Of the remaining 4 patients, 1 had involvement of intrapulmonary lymph nodes in the segment where the primary lesion originated. Another patient had involvement only at the first mediastinal lymph node level, representing a "skipping metastasis". The remaining 2 patients had no lymph node involvement, but had intrapulmonary metastases in the same segments as the primary lesion. We conclude that an extended segmentectomy may be as effective as lobectomy for treatment of peripheral non-small cell lung cancer under 2 cm in diameter without evident lymph node involvement.

Adult↗
PubMed1998

A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese.

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise from interactions between environmental and genetic factors. Endothelial-derived nitric oxide (NO) has been implicated in the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire 26 coding regions. The variant is significantly associated with coronary spasm.

Adult↗
PubMed1998

Primary anastomosis of the trachea: management and pitfalls.

Twenty-four patients with tracheal lesions were managed by various procedures, including primary anastomosis in 16, tracheoplasty in 2, and a terminal tracheostomy in 6. The patients undergoing anastomosis included 4 with primary tumors, 7 with secondary tumors, and 5 with benign stricture. Except for 2 patients, there was no leakage or stenosis after a resection of from two to nine tracheal rings. There were 4 patients in whom the laryngeal nerve was paralyzed on one side prior to resection and then was sacrificed on the other side because of tumor involvement. Because of difficulty in swallowing, the outcome was not satisfactory in the 3 patients despite a good anastomosis. Cricotracheal anastomosis was performed in 3 patients, and thyrotracheal anastomosis in 1. Two patients in whom the trachea and esophagus communicated were treated using pedicled intercostal muscle grafts. Tracheal stenosis can be observed in various pathological conditions. Consequently, the optimal treatment varies from patient to patient according to the type of a disease, the location and extent of a disease, and the condition of the laryngeal nerve, while it is also important to carefully select the most appropriate anesthetic method, approach, and type of reconstruction.

Adolescent↗
PubMed1998

Proposal for reasonable mediastinal lymphadenectomy in bronchogenic carcinomas: role of subcarinal nodes in selective dissection.

OBJECTIVE: The aims of this study were to reveal the characteristics of skipping N2 lung cancer and to develop a more reasonable approach for dissecting mediastinal lymph nodes. METHODS: Of consecutive 956 patients who were operated on for primary lung cancer from 1986 through 1996, 760 (79.5%) had a diagnosis of non-small cell carcinoma and were subjected to complete resection of the tumor together with hilar and mediastinal lymphadenectomy. RESULTS: Of 141 patients with N2 disease, 53 (37.6%) had skipping metastases. Among 78 patients with N2 cancer of the upper lobe, 37 (47.4%) had skipping metastases affecting upper or aortic mediastinal nodes whereas none of them had skipping metastases affecting lower mediastinal nodes. Among 47 patients with N2 cancer of the lower lobe, 13 (27.7%) had skipping metastases affecting mediastinal nodes. Of these 13 patients, 11 (84.6%) had skipping metastases affecting the subcarinal node. The remaining 2 patients had a huge primary tumor. CONCLUSIONS: Dissection of the upper part of the mediastinum including the aortic regions should be performed regardless of the operative appearance when cancer is located in the upper lobe, but it is not required for lower lobe tumors with negative hilar and subcarinal nodes. Dissection of the subcarinal node in patients with an upper lobe tumor is not routinely needed when the nodes in both the hilum and upper mediastinum are intact. We consider that the subcarinal node is of significance and skipping metastases should be defined as metastases that skip the subcarinal node in addition to N1 nodes.

Adenocarcinoma↗
PubMed1998

Operative approach for multiple primary lung carcinomas.

Of 908 patients who underwent operation for primary lung cancer between January 1985 and June 1996, we considered 57 (6.3%) to have a second primary lung cancer, which was synchronous in 28 cases (3.1%) and metachronous in 29 cases (3.2%). Five-year survival for patients with synchronous and metachronous disease from initial treatment of cancer was 70.3% and 66.0%, respectively. Survival after the development of a metachronous lesion was 32.9% at 5 years. Sixteen of the synchronous second tumors (57%) were detected on preoperative radiography or bronchoscopy and 11 (39%) at the time of operation. Survival of patients at stage I or II from treatment of a synchronous lesion (p = 0.002) and of a metachronous second lesion (p = 0.028) was significantly better compared with those at stage III or IV. Therefore it is important to carefully examine a synchronous lesion before and during the operation of a primary lung cancer and to perform close follow-up surveillance for early detection of a metachronous lesion. In treating multiple lung carcinomas consideration should always be given to performing precise staging, aggressive operative approach for early stage, and oncologically sound parenchymal sparing procedures.

Actuarial Analysis↗
PubMed1998

Enhanced production of nitric oxide may be involved in acute hypotension during maintenance hemodialysis.

To investigate the possible involvement of endogenous nitric oxide (NO) in acute hypotension during maintenance hemodialysis, we measured the plasma concentration of the nitrate anion NO3-, a stable metabolite of NO, in 19 patients undergoing hemodialysis. We analyzed heart rate variability to estimate the relationship between autonomic nervous activity and NO production, low-frequency/high-frequency components (L/H) as a parameter of cardiac sympathetic activity, and high-frequency power as a parameter of cardiac vagal activity. Six patients developed severe hypotension (a change in mean blood pressure during dialysis > or = 20 mm Hg), four patients developed mild hypotension (a change in mean blood pressure < or = 19 mm Hg and > or = 1 mm Hg), and nine patients did not develop hypotension. The plasma levels of NO3- before dialysis were markedly elevated in the severely hypotensive group compared with the patients who showed no hypotension (566+/-122 micromol/L v 133+/-38 micromol/L; P < 0.01), and this difference disappeared midhemodialysis and after hemodialysis. The plasma concentration of NO3- before dialysis was significantly associated with both the change in mean blood pressure during dialysis (r= -0.735; P = 0.003) and the mean blood pressure after dialysis (r = -0.675; P = 0.0015). The L/H ratio was inhibited before or after dialysis in the severely hypotensive group compared with the nonhypotensive group, and hypotension during dialysis was correlated with the inhibited L/H ratio before (r = 0.784; P = 0.001) or after (r = 0.822; P = 0.001) dialysis. Plasma NO3- concentrations were correlated with the L/H ratio before (r = -0.553; P = .014) or after (r = -0.546; P = 0.015) dialysis. These results suggest that inhibited sympathetic activity is one of the causes of acute hypotension during dialysis, and the enhanced production of NO is involved in this inhibition of the sympathetic activity in patients having a hypotensive episode during dialysis. The plasma concentration of NO3- before dialysis may be a predictor of the risk of hypotension during dialysis in patients with end-stage renal disease.

Acute Disease↗