Search PubMed⌕ Search

Biomedical subjects

M Oda

Publications and source records attributed to M Oda.

At least 199 records · Page 11Linked to original sources

Expression of phosphotyrosine and SNAP-25 immunoreactivity in grumose (foamy) spheroid bodies suggests axonal regeneration.

To investigate the origin of grumose (foamy) spheroid bodies (GFSB), the expression of two proteins associated with axonal regeneration, i.e., phosphotyrosine and 25-kDa synaptosomal-associated protein (SNAP-25), was immunohistochemically assessed in GFSB in the substantia nigra pars reticulate (SNPR) of progressive supranuclear palsy (PSP). Phosphotyrosine immunoreactive (-IR) and SNAP-25-IR were found in many GFSB. Both were expressed intensely on eosinophilic debris and grumose aggregates in GFSB. Our result suggests that GFSB are structures associated with aberrant sprouting of axons in the degenerated SNPR from other regions such as the globus pallidus to the SNPR, and that the aberrant sprouting may be associated with cell signaling involving tyrosine kinase systems.

Aged↗

Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are characterized by their unique clinical features and neuronal pathology. Although astrocytic plaques and tufts of abnormal fibers have been suggested to be specific histopathologic markers, recent studies have revealed significant clinicopathologic overlap between CBD and PSP. Based on the distinctive camera lucida profile of astrocytic inclusions on Gallyas-Braak silver staining, we found that astrocytic plaques and tufts of abnormal fibers did not coexist in the same patient among 30 cases of clinically diagnosed CBD, PSP and atypical Parkinson's disease. Using Tau immunohistochemistry it was difficult to verify the absence of tufts of abnormal fibers. A morphometric analysis revealed that the two groups classified by the presence or absence of astrocytic plaques and tufts of abnormal fibers exhibited significant differences in the density of ballooned neurons and neurofibrillary tangles and degeneration of the subcortical nuclei. Assessment using the NINDS neuropathologic criteria revealed that the cases with astrocytic plaques and tufts of abnormal fibers closely correspond to CBD and typical PSP, respectively. In addition, the cases lacking either of these two astrocytic inclusions had atypical PSP according to the NINDS criteria, and were associated with novel tau-positive astrocytes (spiny astrocytes). We thus conclude that astrocytic plaques and tufts of abnormal fibers are highly characteristic structures for CBD and typical PSP, respectively. We emphasize the importance of strict differentiation between different astrocytic inclusions not only for diagnosis, but also for further studies for elucidation of their role in the disease mechanisms of CBD and PSP.

Aged↗

Skein-like inclusions in the neostriatum from a case of amyotrophic lateral sclerosis with dementia.

Skeins or skein-like inclusions (SLIs) in motor neurons detected by ubiquitin immunohistochemistry are a characteristic finding of amyotrophic lateral sclerosis (ALS). Here we report ubiquitinated SLIs in the putamen and caudate nucleus from a case of ALS with dementia. A 48-year-old Japanese man developed apathy and amimia. Mental and neurological examinations revealed severe character change, muscle atrophy and fasciculation of the distal upper extremities and the tongue, and an exaggeration of the deep tendon reflex. He subsequently showed dysphagia and dysarthria. He died at the age of 51 years, after a total clinical course of about 2.5 years. By immunohistochemistry, ubiquitin-immunoreactive intraneuronal inclusions were observed in the spinal anterior horn cells, the frontal, temporal and entorhinal cortices, dentate fascia of the hippocampus and the amygdala. In addition, ubiquitinated inclusions were also seen in the putamen and caudate nucleus, which appeared as aggregates of thread-like structures similar to SLIs in the spinal anterior horn neurons. They were not seen on hematoxylin-eosin staining, and they also did not show any argentophilia nor did they react with other antibodies, including antibody against tau protein. To our knowledge, this is the first report of the presence of SLIs in non-motor neurons. Our results thus support the notion that ALS is a multisystem disease, and not simply a disease of the motor neurons.

Amyotrophic Lateral Sclerosis↗

Evidence for involvement of the subcoeruleus nucleus and nucleus raphe magnus in urine storage and penile erection in decerebrate rats.

PURPOSE: Micturition and male sexual activity require the lower urinary tract to function. During the sexual act, micturition must be inhibited and urine stored in the bladder. We studied the role of the brainstem in relation to both micturition/urine storage and penile erection in rats. MATERIALS AND METHODS: Wire electrodes were placed on the dorsal nerve of the penis and microelectrodes for stimulation were introduced into the brainstem in decerebrate male rats. Electrical stimulation was used to locate optimally responding sites by monitoring the isovolumetric intravesical pressure and intracavernous pressure. RESULTS: Electrical stimulation of the dorsal nerve of the penis, the subcoeruleus nucleus in the rostral pons, and the nucleus raphe magnus in the caudal pons increased intracavernous pressure, but inhibited rhythmic bladder contractions. Electrical stimulation of Barrington's nucleus (the pontine micturition center in the rat) in the rostral pons induced bladder contraction. Stimulation of the pontine reticular formation did not increase intracavernous pressure. Acute transection of the thoracic spinal cord eliminated rhythmic bladder contractions, but gave rise to sporadic increments of intracavernous pressure. CONCLUSIONS: This electrophysiological study demonstrated that the subcoeruleus nucleus and nucleus raphe magnus are involved in both urine storage and penile erection, and that their physiological functions are reciprocally controlled; so that erection leads to inhibition of micturition.

Animals↗

Extent of mediastinal node metastasis in clinical stage I non-small-cell lung cancer: the role of systematic nodal dissection.

OBJECTIVE: To determine the extent of lymph node metastasis in clinical stage I non-small-cell lung cancer (NSCLC). METHODS: We performed a retrospective review of 524 patients with clinical stage I NSCLC who underwent lobectomy with systematic nodal dissection. RESULTS: The nodal status was N0 in 409 patients (78%), N1 in 44 (8%), N2 in 67 (13%), and N3 in four (0.8%). Thirty-six patients had single-level mediastinal nodal metastases and 35 had multi-level metastases. The incidence of N2/3 disease in patients with adenocarcinoma/squamous cell carcinoma/other histologic types according to tumor size was 0/0/0%, respectively, in tumors < or = 10 mm in diameter, 12/0/0% in tumors 11-20 mm in diameter, 14/4/23% in tumors 21-30 mm in diameter, and 26/14/20% in tumors >30 mm in diameter. Nodal metastases to the upper mediastinum from middle or lower lobe lesions were frequently observed in 51 N2 adenocarcinomas, whereas those to the lower mediastinum from upper lobe lesions were rare. Of 10 N2 squamous cell carcinomas, seven had regional and three had non-regional nodal metastases. The 5-year survival rate was 68, 43, and 30% in N0, N1, and N2, respectively (P<0.01, N0 versus N1, N0 and N2). CONCLUSIONS: Systematic mediastinal nodal dissection should be routinely performed for clinical stage I lung cancer to ensure the correct nodal status, but it might be dispensable in the patients with peripheral squamous cell carcinoma < or = 20 mm in diameter, with central squamous cell carcinoma < or = 30 mm, and with adenocarcinoma < or = 10 mm. When systematic nodal dissection cannot be performed, the incidence and extent of nodal metastases should be taken account with respect to histologic type, size, and location of the tumor.

Carcinoma, Non-Small-Cell Lung↗

Study on surgical treatment of intractable childhood epilepsy.

We studied the clinical details of 14 children with intractable epilepsies, all of whom underwent epilepsy surgery before age 18 years. All 14 suffered catastrophic seizures, which were resistant to the full range of available medical treatments. The ages at operation ranged from 4 years 7 months to 17 years 2 months, with a mean of 9 years 11 months. In nine patients, the age at onset of epilepsy was less than 2 years. The seizure disorders were classified as temporal lobe epilepsy in two patients, extratemporal lobe epilepsy in 10, and symptomatic generalized epilepsy in two. Eight patients had a hemicorporeal deficit (hemiparesis or hemiplegia) preoperatively. All 14 patients showed localized magnetic resonance imaging (MRI), single photon emission computer tomography (SPECT) and/or positron emission tomography (PET) abnormalities, providing crucial information regarding the epileptic focus. As to the surgical outcomes, four patients became seizure-free and the other 10 showed significant improvement during a mean follow-up period of 2 years 5 months. As to etiology, cortical dysplasia was identified in seven patients. Epilepsy surgery should be considered for intractable childhood epilepsy based on individual clinical characteristics, including seizure status, cognitive development, and evidence indicating location of the seizure focus, rather than age.

Adolescent↗

Involvement of intestinal P-glycoprotein in the restricted absorption of methylprednisolone from rat small intestine.

The interaction between steroid hormones and intestinal P-glycoprotein was investigated by measuring intestinal absorption from rat small intestine in situ. Prednisolone and hydrocortisone were rapidly absorbed from the entire small intestine. In contrast, methylprednisolone absorption was significantly retarded in jejunum and ileum by an intestinal efflux system. In the presence of verapamil an quinidine, the retarded absorption of methylprednisolone was completely recovered, suggesting that P-glycoprotein is responsible for the unique features of methylprednisolone absorption. A requisite for the substrate of intestinal P-glycoprotein seemed to be 6 alpha-methyl group in the steroid structure. Substrate specificity of intestinal P-glycoprotein to steroid hormones was shown to be in part different from those in other tissues such as adrenal gland. Little of all three steroid hormones disappeared in the supernatant of mucosal homogenate from rat small intestine, indicating that intestinal metabolism of these steroid hormones was relatively small.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Inhibition of inducible nitric oxide synthase delays gastric ulcer healing in the rat.

We sought to clarify the role of nitric oxide (NO) generated from inducible NO synthase (iNOS) during healing of rat gastric ulcers. After gastric ulcers were induced by acetic acid, rats were treated with vehicle, N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and dexamethasone (Dex) by gastric intubation twice a day for 3 days to 1 week. L-NAME significantly delayed healing compared with vehicle. AG and Dex significantly reduced ulcer size 3 days after ulcer induction but did not further reduce ulcer size 1 week after induction. iNOS expression was present in inflammatory cells, some epithelial cells, and in vascular smooth muscle in the regenerating mucosa of the vehicle-treated group. However, the number of iNOS-positive inflammatory cells increased in the AG- and L-NAME-treated groups. AG and L-NAME significantly increased the number of inflammatory cells with endogenous peroxidase and significantly reduced the number of apoptotic inflammatory cells compared with vehicle. In conclusion, inhibition of iNOS increases the number of inflammatory cells in the ulcer margin and delays ulcer healing. These observations suggest that NO generated from iNOS not only participates in ulcer formation but also plays a beneficial role in ulcer healing, in part by the exclusion of iNOS-positive inflammatory cells from the regenerating mucosa.

Animals↗

Effect of combined administration of lansoprazole and sofalcone on microvascular and connective tissue regeneration after ethanol-induced gastric mucosal damage.

We undertook the present study to clarify the alteration of localization of basic fibroblast growth factor (bFGF), endothelial cells, and myofibroblasts in the healing of ethanol-induced gastric mucosal damage by the combined administration of lansoprazole and sofalcone. Wistar strain male rats were used. Ethanol 50% was given through orogastric intubation. Thirty minutes later, an aqueous solution of lansoprazole, sofalcone, a combination of lansoprazole and sofalcone, or physiologic saline was given orally. The stomach was removed and the localization of bFGF, myofibroblast, and endothelial cells was examined using monoclonal antibodies. Some rats were pretreated with indomethacin to rule out the effect of endogenous prostaglandin. The combined administration of lansoprazole and sofalcone brought about increased concentrations and immunoreactive areas of bFGF and a greater number of endothelial cells, compared with the ethanol-alone treatment. The number of myofibroblasts increased more significantly in the group treated with a combination of agents than in that treated with ethanol alone, ethanol plus sofalcone, or ethanol plus lansoprazole. Indomethacin pretreatment partly abolished the effects of single and combined administration of these agents. In conclusion, the mixed administration of lansoprazole and sofalcone accelerated the microvascular and connective tissue regeneration during the healing of ethanol-induced gastric mucosal damage.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Appearance of myofibroblasts in the gastric mucosa after ingestion of ethanol and lansoprazole with reevaluation of the mucoid cap.

The mucoid cap is important in the restitution of surface epithelial cells of the gastric mucosa. We conducted the present study to clarify the relationship of the mucoid cap and the myofibroblasts in the course of healing of the gastric mucosa with ethanol-induced damage. The effect of lansoprazole on ulcer healing was also evaluated. Wistar strain male rats were administered ethanol (50%) by gastric intubation. Thirty minutes later, either an aqueous solution of lansoprazole (LPZ; 10 mg/100 g of body weight), or the same amount of physiological saline was administered by gastric intubation. Localization of the myofibroblasts was evaluated at 1, 3, and 12 hr after LPZ treatment, and compared with the number and localization of cells positive for rhodamine-phalloidin. The concentration of basic fibroblast growth factor (FGF) was determined by EUSA. We observed PR 2D3-immunoreactive cells in the lamina propria mucosae of the control fundus that were weakly positive or negative for rhodamine-phalloidin. Erosive lesions reaching more than half of the whole gastric mucosal layer were induced 1 hr after ethanol ingestion. An abundance of PR 2D3 and rhodamine-phalloidin double-positive cells was present in the lamina propria mucosae just below the erosive lesion. The administration of LPZ brought about an increase in bFGF concentration, an acceleration of ulcer healing, and an increase in immunoreactivity to PR 2D3. In conclusion, LPZ strongly influenced the healing of gastric mucosal damage related to ethanol administration, possibly through an increase in the concentration of bFGF. The immunophenotype of the myofibroblasts changed to the muscle type during healing, suggesting an involvement of these cells in ulcer healing.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Non-synchronous double adenoma of the parathyroid gland.

A 46-year-old female underwent an excision of a parathyroid adenoma diagnosed as recurrent primary hyperparathyroidism 24 years after the initial excision of a parathyroid adenoma. We report a case of non-synchronous double adenomas of the parathyroid glands documented histopathologically.

Adenoma↗

Cell growth inhibition and DNA incorporation of mitomycin C in cell culture.

The present study was performed to clarify the effects of a 4-min exposure of mitomycin C (MMC) on cell growth, the cell cycle and MMC dose incorporated into DNA, using Chang's cultured human conjunctival cells. A low dose of MMC ranging from 0.00025 to 0.004% showed dose-dependent cytotoxicity when cell growth was active. Fifty percent cell viability was found when cells were treated with 0.001% MMC. A flow cytometer showed that 0.001% MMC inhibited the DNA synthetic phase. After 0.04% MMC was exposed to 3 x 10(6) cells and immediately rinsed, DNA was isolated to measure the dose of MMC detected from DNA. The total amount of DNA was 7 micrograms from which 3 micrograms of MMC was detected by high performance liquid chromatography. The above results revealed that the lowest concentration of MMC which caused 50% cell viability and cell cycle inhibition was 0.001% and that MMC was rapidly incorporated into DNA.

Cell Cycle↗

Molecular cloning and characterization of a new member of the rat placental prolactin (PRL) family, PRL-like protein H.

The rat placental PRL family consists of molecules structurally similar to PRL and GH, and to date nine members have been identified. In the course of investigating late stage specific placental PRL family expression by differential display, we have isolated a complementary DNA encoding a new molecule that is highly homologous to PRL-like protein C (PLP-C) and PLP-D, and named this molecule PLP-H. The complementary DNA encoded a mature protein of 239 amino acids, including a 31-amino acid signal sequence. Sequence comparison between PLP-H and other members of the placental PRL family showed that PLP-H is highly homologous to PLP-C and PLP-D (78% and 67% homology at the amino acid level, respectively). Expression of PLP-H was similar to that of PLP-C and PLP-D; PLP-H messenger RNA (mRNA) first appeared on day 14 of pregnancy, and its expression increased until term. RT-PCR analysis showed that PLP-H as well as PLP-C and PLP-D are expressed in all rat strains examined, confirming that PLP diversity is not due to strain differences. In situ hybridization analysis indicated that PLP-H mRNA is specifically expressed in spongiotrophoblast cells and in trophoblast giant cells of the placental junctional zone. Differentiated Rcho-1 cells also expressed PLP-H mRNA, whereas undifferentiated Rcho-1 cells did not. PLP-H seems to exist as a secretory protein because its N-terminal sequence is identical to that of GH/PRL-like molecule secreted from placental explants. PLP-H contains two putative N-glycosylation sites and eight cysteine residues, of which six are highly conserved in the placental PRL family. We prepared a recombinant protein for PLP-H together with PLP-D using a COS7 transfection system. Purified PLP-H showed two bands with molecular masses of 27 and 29 kDa. Only the 27-kDa protein was detected after N-glycosidase treatment, indicating that PLP-H is a glycoprotein. PLP-H and PLP-D did not stimulate the proliferation of Nb2 lymphoma cells or the phosphorylation of Janus kinase-2 and signal transducer and activator of transcription-5. These data indicate that PLP-H and PLP-D are nonlactogenic hormones. Thus, we have cloned a new member of the PLP subfamily, PLP-H, which has features in common with PLP-C and PLP-D.

Amino Acid Sequence↗

Effect of side chains including the N-methyl-tetrazole-thiol group of beta-lactam antibiotics on transport in cultured kidney epithelial cells LLC-PK1.

In this study, the transcellular transport characteristics of four beta-lactam antibiotics (cefotaxime, cefmenoxime, cefmetazole, and cefotiam) were investigated in a kidney epithelial cell line LLC-PK1, especially focusing on the effect of the N-methyl-tetrazole-thiol (NMTT) group attached to 7-amino-cephalosporanic acid. There were no directional differences between the apical-to-basolateral and basolateral-to-apical transport of cefotaxime, cefmenoxime, and cefmetazole, suggesting that the NMTT group does not influence the transcellular transport behaviors of beta-lactam antibiotics. In contrast, cefotiam transport across LLC-PK1 cell monolayers was 1.3-fold greater in the basolateral-to-apical direction than in the apical-to-basolateral direction. It is considered that the ionization of nitrogen in the N-dimethylaminoethyl group attached to NMTT is a factor in the secretory-oriented movement of cefotiam. The transcellular transport of cefotiam in both directions was significantly depressed at a low temperature (4 degrees C) and by 2,4-dinitrophenol. The basolateral-to-apical transport of cefotiam was also shown to be concentration-dependent. These results suggest that a specialized transport process might participate in the transcellular transport of cefotiam. The lipophilicities of these beta-lactam antibiotics were not correlated to the degree of transcellular transport, directly.

Animals↗

Evaluation of the role of N-linked oligosaccharides in rat placental lactogen action by site-directed mutagenesis.

To evaluate the role of N-linked oligosaccharides in the molecular action of rat placental lactogen (PL), recombinant PL-Im (recPL-Im) and three recPL-Im mutants were produced in COS-7 cells. The mutants, carrying Gln substitutions of Asn at putative N-glycosylation sites, were generated via site-directed mutagenesis, i.e. two single mutants (N79Q, N128Q) and one double mutant (N79Q/N128Q). Western blot analysis revealed that wild type recPL-Im had a molecular mass of 34 kDa , which was reduced to 29 kDa by tunicamycin present during expression. N79Q and N128Q had a lower molecular mass than the wild type, and a further decrease was observed for N79Q/N128Q. PL-Im was therefore N-glycosylated at both Asn79 and Asn128. Treatment of the wild type with neuraminidase caused a reduction in molecular mass, indicating that the N-linked oligosaccharides contained N-acetylneuraminic acids. In the Nb2 cell bioassay for lactogenic hormones, recPL-Im and its mutants all had growth-promoting activity but there was a decline in the growth-stimulating potency following decreases in N-glycosylation, i.e. the order of relative potencies was the wild type>N128Q> N79Q>N79Q/N128Q, suggesting that the N-linked oligosaccharides are important in the mitogenic action of the PL-Im. Wild type and all mutants had rat PRL receptor (PRL-R)-binding activity in radioreceptor assays and stimulated JAK2 phosphorylation in Nb2 cells. Interestingly however, the binding activity to PRL-R and phosphorylation of JAK2 was similar in the wild type and mutants, and these results are not in accord with the biological activity. In conclusion, the study suggested that PL-Im has two N-linked oligosaccharides which are involved in its biological activity. The ability of PL-Im to bind PRL-R and activate JAK2 appears to be independent of the N-glycosylation.

Animals↗

Signal-averaged electrocardiogram shows a heart rate dependent diurnal variation in healthy subjects.

It has not been determined if signal-averaged electrocardiograms (SAECGs) have a diurnal variation. We recorded 3-channel 24-hour ECGs in 30 healthy volunteers and calculated the following parameters for the first 500 sec of every hour over the 24-hour period: the mean heart rate, the filtered QRS duration (f-QRS), the root-mean-square voltage of the signals in the last 40 msec of the QRS (RMS40), and the duration of low-amplitude signals (< 40 microV) in the terminal portion of the QRS (LAS40). Heart rate and RMS40 increased in the daytime compared with the nighttime; f-QRS and LAS40 increased during the nighttime hours. The f-QRS and LAS40 were negatively correlated with heart rate in all and 22 (73%) of 30 subjects, respectively, and RMS40 was positively correlated with heart rate in 21 subjects (70%). In conclusion, SAECGs exhibit a clear diurnal variation in healthy subjects, which is closely related to changes in heart rate.

Adult↗

Mineral recovery system for a Closed Ecology Experiment Facility (CEEF).

A unique recovery system, which consists of electrodialysis (ED) and crystallization processes, is proposed for NaCl (salt) from waste water after oxidation of urine. NaCl recovery characteristics from the oxidized urine, which contains KCl and NO3- impurities, were experimentally evaluated. Concentrated NaCl/KCl mixed solution was obtained using the ED process from simulated oxidized urine and sweat. Large amounts of NO3- were contained in the concentrated solution. After the crystallization process, NaCl salt of 90% purity, containing less than 5% NO3-, could be recovered by crystallization from the solution at 90 degrees C because NaNO3 or KNO3 salt has high solubility in water at that temperature. The results show that the proposed mineral recovery system can recover NaCl from waste water in the CEEF.

Chemical Precipitation↗