Biomedical subjects

M Umeda

Publications and source records attributed to M Umeda.

At least 91 records · Page 5Linked to original sources

PubMed1999

Molecular characterization of mitotic cyclins in rice plants.

Cyclins are known to activate cyclin-dependent protein kinases, which are essential for cell cycle progression in eukaryotes. We isolated full-length cDNAs encoding rice mitotic cyclins named CycA1; os; 1 and CycB2;os;1, which are related to A- and B-type cyclins, respectively, from animals. To characterize the function of these mitotic cyclins, as well as that of another B-type cyclin, CycB2;os;2, each cDNA was introduced into yeast cells. When cDNAs encoding CycA1;os;1, CycB2;os; or CycB2;os;2 were overexpressed in the yeast mutant DLI, which is deficient in G1 cyclins, the mutant phenotype was rescued, indicating that these mitotic cyclins are functional in yeast cells. When the cDNA encoding CycB2;os;1 was expressed in the wild-type yeast strain, the cells lost the ability to grow, whereas the expression of either cycA1;os: 1 or cycB2;os;2 did not inhibit growth. In situ hybridization of these mitotic cyclin genes with rice root apices and counterstaining of chromosomes with a DNA-specific dye revealed that cycA1;os;1 is expressed from the G2 phase to the early M phase, while transcripts of cycB2:os;1 and cycB2;os;2 accumulated until the end of mitosis. Our results indicate that these B2-type cyclins may be involved in the control of mitosis, in combination with a G2/M-phase CDK.

Amino Acid Sequence↗

PubMed1999

Membrane phospholipid dynamics during cytokinesis: regulation of actin filament assembly by redistribution of membrane surface phospholipid.

To study molecular motion and function of membrane phospholipids, we have developed various probes which bind specifically to certain phospholipids. Using a novel peptide probe, RoO9-0198, which binds specifically to phosphatidylethanolamine (PE) in biological membranes, we have analyzed the cell surface movement of PE in dividing CHO cells. We found that PE was exposed on the cell surface specifically at the cleavage furrow during the late telophase of cytokinesis. PE was exposed on the cell surface only during the late telophase and no alteration in the distribution of the plasma membranebound peptide was observed during the cytokinesis, suggesting that the surface exposure of PE reflects the enhanced transbilayer movement of PE at the cleavage furrow. Furthermore, cell surface immobilization of PE induced by adding of the cyclic peptide coupled with streptavidin to prometaphase cells effectively blocked the cytokinesis at late telophase. The peptide-streptavidin complex bound specifically to cleavage furrow and inhibited both actin filament disassembly at cleavage furrow and subsequent plasma membrane fusion. Binding of the peptide complex to interphase cells also induced immediate disassembly of stress fibers followed by assembly of cortical actin filaments to the local area of plasma membrane where the peptide complex bound. The cytoskeletal reorganizations caused by the peptide complex were fully reversible; removal of the surface-bound peptide complex by incubating with PE-containing liposome caused gradual disassembly of the cortical actin filaments and subsequent formation of stress fibers. These observations suggest that the redistribution of plasma membrane phospholipids act as a regulator of actin cytoskeleton organization and may play a crucial role in mediating a coordinate movement between plasma membrane and actin cytoskeleton to achieve successful cell division.

Actins↗

PubMed1999

Effect of monochloramine on recovery of gastric mucosal integrity and blood flow response in rat stomachs--relations to capsaicin-sensitive sensory neurons.

Gastric mucosal blood flow (GMBF) response and the recovery of gastric mucosal integrity were investigated in anesthetized rat stomachs after damage by monochloramine (NH2Cl), in comparison with 20 mM taurocholate Na (TC). A rat stomach was mounted in an ex-vivo chamber, and the mucosa was exposed to 50 mM HCl during a test period. Mucosal application of 20 mM TC for 10 min caused a marked reduction of transmucosal potential difference (PD), but the PD recovered rapidly without development of gross lesions 90 min later. In contrast, the exposure of the mucosa to NH2Cl (5 to approximately 20 mM) produced a concentration-dependent decrease in gastric PD, and the values remained lowered even 90 min after removal of the agent, resulting in severe hemorrhagic damage in the stomach. TC caused a considerable H+ back-diffusion, followed by an increase in the GMBF. In the mucosa damaged by NH2Cl, such GMBF responses were not observed, except for the temporal increase during the exposure, although similar degrees of H+ back-diffusion were observed following NH2Cl treatment. In addition, the prior exposure of the mucosa to NH2Cl significantly attenuated gastric hyperemic response induced by capsaicin but not by misoprostol (a PGE1 derivative) or NOR-3 (a NO donor). Chemical ablation of capsaicin-sensitive sensory neurons had no effect on the PD reduction caused by TC but totally attenuated the GMBF response, resulting in hemorrhagic damage in the stomach. These results suggest that NH2Cl delayed the recovery of the mucosal integrity in the stomach after damage, and this effect may be attributable, at least partly, to the impairment of gastric hyperemic response associated with H+ back-diffusion, probably due to dysfunction of capsaicin-sensitive sensory neurons.

Animals↗

PubMed1999

Tumor-doubling time and onset of pulmonary metastasis from adenoid cystic carcinoma of the salivary gland.

Adenoid cystic carcinoma (ACC), an uncommon malignancy in the head and neck region, invades diffusely and often metastasizes to the lung, although the growth rate is very slow. A retrospective study was conducted in 30 patients with ACC to ascertain the frequency of pulmonary metastasis, the doubling time of metastatic tumor deposits, and the time of onset for pulmonary metastasis. The following results were obtained: (1) Of 30 patients with ACC, 21 had pulmonary metastases (4 initially and 17 during observation), 7 were free of metastases but have not been observed for 5 years, and 2 were free of metastases for more than 5 years but less than 10 years after the initial treatment. The cumulative metastasis rate at 5 and 10 years for this group of patients was 70% and 100%, respectively. (2) Patients with T1 or T2 tumors that have a tubular or cribriform histopathologic pattern showed pulmonary metastases about 20 months later than those with T3 or T4 tumors and a solid pattern. However, the final metastasis rate did not differ between the 2 groups after a long period. (3) The tumor doubling time of the metastatic deposits of ACC was 86 to 1064 days with an average of 393 days, which was much longer than that of most other malignant neoplasms reported previously. (4) The time of onset of pulmonary metastasis was calculated to be much earlier (average of 227 months) before the first visit. These findings suggest that the treatment method for ACC should be chosen with the consideration that many of the patients may have occult pulmonary metastases at the time of their initial evaluation.

Carcinoma, Adenoid Cystic↗

PubMed1999

A high serum soluble Fas/APO-1 level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma.

Soluble Fas (sFas) in the serum is believed to be able to inhibit apoptosis of lymphocytes. It has been reported that the serum sFas level is increased in various diseases, including malignant lymphoma and systemic lupus erythematosus. We studied the association between sFas and the prognosis of patients with aggressive non-Hodgkin's lymphoma (NHL). Compared with normal controls, the serum sFas level was increased significantly in patients with aggressive NHL and adult T cell leukemia/lymphoma. Among patients with aggressive NHL, the complete remission rate was significantly decreased in the subgroup having high serum sFas levels. Both the overall survival rate and the disease-free survival (DFS) rate were significantly lower for this subgroup than for patients with low serum sFas levels. The 5-year survival rates estimated by the Kaplan-Meier method for patients with high and low serum sFas levels were 27.6% and 68.3%, respectively (P = 0.0001). The 5-year DFS rates estimated for patients with high and low serum sFas levels were 44.7% and 71.9%, respectively (log-rank test: P = 0.0023, and generalized Wilcoxon test: P = 0.0014). Among patients with a low and low-intermediate risk group according to the International Prognostic Index (IPI), the 5-year survival rates for low and high serum sFas subgroups were 72.8% and 42.0%, respectively, showing a significant difference (Wilcoxon test: P = 0.0163, log-rank test: P = 0.0115). Among patients with a high-intermediate and high risk group, the 5-year survival rates for low and high serum sFas subgroups were 51.6% and 17.4%, respectively, again showing a significant difference (Wilcoxon test: P = 0.0001, log-rank test: P = 0.0002). Multivariate analysis of a series of prognostic factors, including the five used to calculate the IPI, showed that the serum sFas level was an independent prognostic factor for the overall survival. Based on these results, a serum sFas level of 10 ng/ml or more can be considered to indicate a poor prognosis in patients with advanced NHL, and this finding may be useful for developing strategies for further treatment.

Adolescent↗

PubMed1999

Ultrastructural localization of E-cadherin and alpha-/beta-catenin in adenoid cystic carcinoma.

AIMS: To investigate the disturbance of intercellular adhesion in adenoid cystic carcinoma (ACC), we examined the ultrastructural localization of E-cadherin (E-cad), alpha-catenin (alpha-cat) and beta-catenin (beta-cat) in ACC, and compared it with that in the normal labial gland. METHODS AND RESULTS: Using immuno-electron microscopy, in the normal labial gland, E-cad was found to be uniformly distributed along the plasmalemma, where cells were in close contact with each other, with junctional complexes, desmosomes and interdigitations; expression of alpha-cat and beta-cat was also detected. In ACC, which was classified into tubular, cribriform and trabecular types, E-cad expression seemed not to be uniform, but was observed to be along the plasmalemma where cell-to-cell contact was made. On the other hand, expression of alpha-cat or beta-cat was uneven in the trabecular-type cells which were very slender and grew in an infiltrative scattered pattern into the extracellular matrix; that was absent in the cribriform-type cells which made contact with each other mostly at the tip of the cytoplasmic processes. CONCLUSION: These findings suggest that the neoplastic cells of ACC express E-cad for use in intercellular adhesion, but the cadherin-catenin complex might not operate properly, which is the cause of neoplastic cell dissociation, followed by invasion and metastasis.

Adult↗

PubMed1999

Effect of lafutidine, a novel histamine H2-receptor antagonist, on monochloramine-induced gastric lesions in rats: role of capsaicin-sensitive sensory neurons.

BACKGROUND: Lafutidine ((+/-)-2-(furfurylsulfinyl)-N-(4-(4-(piperidinomethyl)-2-pyr idyl)oxy-(Z)-2-butenyl)acetamide) is a novel histamine H2-receptor antagonist and has been shown to exhibit a potent gastroprotective activity in addition to its antisecretory action. In the present study, we examined the effects of lafutidine on the mucosal ulcerogenic and potential difference (PD) responses induced by monochloramine (NH2Cl) in rat stomachs. METHODS: Oral administration of NH2Cl at 120 mmol/L produced haemorrhagic lesions in the stomach in unanaesthetized rats. RESULTS: Lafutidine (3-30mg/kg), given p.o., showed a dose-dependent and significant inhibition against damage caused by NH2Cl: the effect was significant at 10 mg/kg or greater but disappeared almost totally in the sensory deafferented animals following capsaicin pretreatment. Likewise, capsaicin (10 mg/kg, p.o.), but not cimetidine (100 mg/kg, p.o.) exhibited a potent protection against NH2Cl-induced gastric lesions. Topical application of NH2Cl (10 mmol/L) reduced transmucosal PD in ex-vivo stomachs of anaesthetized rats, but this PD response was also prevented by pre-exposure to lafutidine, in a dose-dependent and sensory neuron-sensitive manner. Mucosal exposure to NH4OH (60 mmol/L) also caused PD reduction in ex-vivo stomachs made ischaemic by bleeding from the carotid artery (1 mL/100 g bodyweight), resulting in severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischaemia were attenuated by prior application of lafutidine as well as taurine, a scavenger of NH2Cl. The former effect was, again, dependent on the sensory neurons. Intraluminal capsaicin but not cimetidine was also effective in preventing a PD response to NH2Cl. CONCLUSIONS: These results suggest that lafutidine, but not cimetidine, protects the stomach against NH2Cl, whether occurring endogenously or administered exogenously and that this action may be mediated by capsaicin-sensitive sensory neurons.

Acetamides↗

PubMed1999

Lymph node metastases in hamster tongue cancer induced with 9,10-dimethyl-1,2-benzanthracene: association between histological findings and the incidence of neck metastases, and the clinical implications for patients with tongue cancer.

An experimental study was carried out in hamster tongue cancer induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) to examine the association between the histological features and the incidence of lymph node metastases. Squamous cell carcinoma was induced in 64 of 71 hamsters exposed to DMBA 3 times weekly for a period of 10-24 weeks, and lymph node metastases were found in 8 necks. Various histological variables in the primary lesion were examined, and the mode of invasion, degree of keratinization, and stage of invasion were found to be closely related to the development of neck metastases. We then did a prospective study in 37 human patients with T1-2 tongue cancer, which also showed a close association between the incidence of neck metastases and the histological variables of mode of invasion and degree of keratinization. These experimental and clinical studies suggest that the mode of invasion and degree of keratinization may be risk factors for neck metastases that are independent of T stage, and that the indications for elective neck dissection should be re-evaluated in that light.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

A monoclonal antibody, 3A10, recognizes a specific amino acid sequence present on a series of developmentally expressed brain proteins.

Immunoblotting showed that a monoclonal antibody, 3A10, binds to a series of rat brain-specific antigens with molecular masses of 150-, 120-, 118-, 106-, 104-, 79-, and 77-kDa. The expression of 3A10 antigens is dependent on the developmental stage of the brain; only the 106-kDa antigen is detected during embryonic stages of rat brain development, while the expression of the remaining 6 antigens starts after birth and reaches a maximum during postnatal days 15-21. Detection of the 3A10 antigens in cultured neuronal and glial cells derived from cerebral cortices of rat brain at embryonic day 18 showed that the 77-, 79-, 106-, and 150-kDa antigens are specifically expressed in neuronal cells. The 77-kDa antigen was purified and identified as synapsin I by amino acid sequence analyses of the peptide fragments isolated after Achromobacter protease I treatment. During the isolation of 3A10-reactive proteins by immunological screening of cDNA libraries constructed from adult rat brain, we found that all of the 3A10-reactive clones contain nucleotide sequences encoding the unique amino acid sequence TRSP(S, R,G)P. Analyses of 3A10-binding to various synthetic peptides showed that the monoclonal antibody recognizes a specific conformational structure formed by either the TRSPXP sequence or similar amino acid sequences that are expressed on a series of developmentally expressed brain proteins.

Amino Acid Sequence↗

PubMed1999

Differential expression of genes for cyclin-dependent protein kinases in rice plants.

Cyclin-dependent protein kinases (CDKs) play key roles in regulating the eukaryotic cell cycle. We have analyzed the expression of four rice (Oryza sativa) CDK genes, cdc2Os1, cdc2Os2, cdc2Os3, and R2, by in situ hybridization of sections of root apices. Transcripts of cdc2Os1, cdc2Os2, and R2 were detected uniformly in the dividing region of the root apex. cdc2Os1 and cdc2Os2 were also expressed in differentiated cells such as those in the sclerenchyma, pericycle, and parenchyma of the central cylinder. By contrast, signals corresponding to transcripts of cdc2Os3 were distributed only in patches in the dividing region. Counterstaining of sections with 4', 6-diamidino-2-phenylindole and double-target in situ hybridization with a probe for histone H4 transcripts revealed that cdc2Os3 transcripts were abundant from the G2 to the M phase, but were less abundant or absent during the S phase. The levels of the Cdc2Os3 protein and its associated histone H1-kinase activity were reduced by treatment of cultured cells with hydroxyurea, which blocks cycling cells at the onset of the S phase. Our results suggest that domains other than the conserved amino acid sequence (the PSTAIRE motif) have important roles in the function of non-PSTAIRE CDKs in distinct cell-cycle phases.

Amino Acid Sequence↗

PubMed1999

Detection of Treponema socranskii associated with human periodontitis by PCR.

A PCR technique was used to detect and identify Treponema socranskii associated with periodontitis. A species-specific forward primer was designed for a variable region within its 16S rRNA gene and was used in conjunction with a conserved reverse primer. This primer pair was tested for specificity against 44 oral bacterial strains. Sensitivity was determined using a serial dilution of T. socranskii cells. Amplification products were obtained from all T. socranskii strains tested, but not from other oral bacteria associated with periodontal disease. The detection limit of PCR was 5 T. socranskii cells per PCR. T. socranskii was detected by PCR in subgingival plaque and saliva samples from patients with periodontitis.

Adult↗

PubMed1999

Phylogenetic analysis of saccharolytic oral treponemes isolated from human subgingival plaque.

A total of 74 strains of oral treponemes, which were isolated from subgingival plaque samples from patients with periodontitis, were taxonomically studied on the basis of biochemical characteristics, DNA-DNA hybridization, and 16S rRNA gene sequences. These organisms fermented carbohydrates and required rumen fluid or short-chain volatile fatty acids for growth. The isolates were divided into seven subgroups based on their biochemical characteristics. The levels of DNA relatedness among the representative strains of each subgroup and Treponema socranskii (including three subspecies) were greater than 78%, while the levels of DNA relatedness among these strains and other Treponema species, including T. denticola and "T. vincentii", were less than 15%. DNA-DNA hybridization indicated that all subgroups belonged to T. socranskii. This result correlated well with the cluster on the phylogenetic trees based on 16S rRNA sequences.

Base Composition↗

PubMed1999

Response and adverse drug reactions to combination chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma: comparison of CHOP, COP-BLAM, COP-BLAM III, and THP-COPBLM.

We retrospectively compared therapeutic results and adverse events in 198 elderly patients (> or = 70 yr old) with aggressive non-Hodgkin's lymphoma diagnosed between 1981 and 1995 who underwent CHOP, COP-BLAM, COP-BLAM III, or THP-COPBLM chemotherapy. Complete remission (CR) was achieved in 138 patients (69.7%). The CR rate was 47.0% for CHOP, 76.3% for COP-BLAM, 67.9% for COP-BLAM III, and 74.4% for THP-COPBLM therapy (p = 0.013). The 5-yr survival rate was 37.0% for CHOP, 49.0% for COP-BLAM, and 53.5% for COP-BLAM III. The event-free survival rate showed no significant differences between the four treatments. Adverse events of Grade 3 or worse were commonly anemia or granulocytopenia in patients receiving THP-COPBLM therapy. Cardiac sympathetic dysfunction and cardiac mitochondrial damage were less common with pirarubicin than with doxorubicin. For elderly patients, it is better to select therapy with as few adverse events as possible based on the complications and medical history of the individual patients.

Aged↗

PubMed1999

Relationship between herpesviruses and adult periodontitis and periodontopathic bacteria.

BACKGROUND: Various mammalian viruses and specific bacteria seem to play important roles in the pathogenesis of human periodontitis. This study examined the relationship between subgingival herpesviruses and periodontal disease and potential periodontopathic bacteria in 140 adults exhibiting either periodontitis or gingivitis. METHODS: A nested-polymerase chain reaction (PCR) method determined the presence of Epstein-Barr virus type 1 and type 2 (EBV-1, EBV-2), human cytomegalovirus (HCMV), and herpes simplex virus (HSV) and a 16S rRNA PCR detection method identified Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola. RESULTS: Using a logistic analysis, EBV-1 showed significant positive association with P. gingivalis (odds ratio [OR] 3.37), and with coinfections of P. gingivalis and P. intermedia (OR 4.03); P. gingivalis and B. forsythus (OR 3.84); P. gingivalis and T. denticola (OR 4.17); P. gingivalis, B. forsythus, and T. denticola (OR 4.06); and P. gingivalis, P. nigrescens, and T. denticola (OR 3.29). EBV-1 also showed positive association with severe periodontitis (OR 5.09), with increasing age (OR 1.03), and with periodontal probing depth at the sample sites (OR 1.77). HCMV was positively associated with coinfections of P. gingivalis and P. nigrescens (OR 3.23); P. gingivalis, B. forsythus, and P. nigrescens (OR 3.23); and P. gingivalis, P. nigrescens, and T. denticola (OR 2.59); with severe periodontitis (OR 4.65); and with age (OR 1.03). Patients with mixed viral infections revealed significant associations with P. gingivalis (OR 2.27), and with coinfections of P. gingivalis and B. forsythus (OR 2.06); P. gingivalis and P. nigrescens (OR 2.91); P. gingivalis, B. forsythus, and P. nigrescens (OR 2.91); and P. gingivalis, P. nigrescens, and T. denticola (OR 2.70) with the clinical diagnosis of slight (OR 3.73), moderate (OR 3.82), or severe periodontitis (OR 4.36), and with probing depth at the sample sites (OR 1.39). HSV and EBV-2 showed no significant associations with any of the variables tested. CONCLUSIONS: The results indicate that subgingival EBV-1, HCMV, and viral coinfections are associated with the subgingival presence of some periodontal pathogens and periodontitis. Herpesviruses may exert periodontopathic potential by decreasing the host resistance against subgingival colonization and multiplication of periodontal pathogens.

Actinobacillus Infections↗

PubMed1999

Effect of initial periodontal therapy on the frequency of detecting Bacteroides forsythus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans.

BACKGROUND: Porphyromonas gingivalis, Bacteroides forsythus, and Actinobacillus actinomycetemcomitans have been described as periodontopathic bacteria, and their presence in subgingival pockets can lead to development of periodontal disease. Until now, clinical parameters have been used to evaluate the effect of conventional periodontal treatment without microbiological parameters. The present study examined the microbiological effects of initial periodontal therapy using DNA probes and the polymerase chain reaction (PCR). METHODS: Twenty-six patients with periodontitis, 10 males and 16 females, were given instructions regarding oral hygiene, then thoroughly treated by conventional scaling and root planing. Bacterial samples were collected on paper points from 4 sites per patient at baseline and after initial therapy (total: 104 sites). Clinical parameters including probing depth, attachment level, and bleeding on probing were also recorded for each site at baseline and after therapy. A DNA probe kit was used to monitor the frequency of B. forsythus, P. gingivalis, and A. actinomycetemcomitans, the last of which was identified by PCR. RESULTS: At baseline, B. forsythus was the bacterium most frequently detected. DNA probe analysis also showed that more than half of the sites were colonized by both B. forsythus and P. gingivalis. Initial therapy resulted in significant clinical improvement such as significant reduction in the frequency of B. forsythus and P. gingivalis detected using the DNA probe. A. actinomycetemcomitans was difficult to detect using the DNA probe, but PCR indicated that levels of A. actinomycetemcomitans did not significantly decrease. CONCLUSIONS: These results indicate that initial conventional therapy can eliminate B. forsythus and P. gingivalis, but not A. actinomycetemcomitans. When levels of these bacteria decreased to below-detectable levels, clinical improvement was significant. These results indicate that monitoring levels of these three periodontopathic bacteria may render periodontal therapy more effective and accurate.

Adolescent↗

PubMed1999

[COP-BLAM therapy for a Hodgkin's disease in the elderly].

Hodgkin's disease (HD) is a disorder with a better prognosis than non-Hodgkin's lymphoma and it predominantly affects young persons. In association with the aging of the population, however, HD has been increasing among persons aged 65 years and over in recent years. We used the COP-BLAM regimen to treat elderly patients with HD, and responses and adverse reactions were investigated. A total of 14 patients with HD treated at our department between April 1987 and December 1997 were included in this study. The patients were 8 men and 6 women aged 65 years or older, with a median age of 68 years. Five patients with clinical stage I or II disease, who had factors indicating a poor prognosis, received 3 courses of the COP-BLAM regimen with additional regional therapy of the involved field (IF). Six courses of COP-BLAM were administered to 9 patients with stage III or IV disease. The treatment was evaluable in all patients. Treatment achieved a complete remission (CR) in 12 (85.7%) of the 14 patients and a partial remission in 2 (14.3%). The CR rate was 100% for stage I or II and 77.8% for stage III or IV. The overall 5-year survival rate was 76.2% and overall disease-free 5-year survival rate was 75.7%. Adverse reactions included grade 3 or higher leukopenia in 35.7% and grade 3 or higher thrombocytopenia in 7.1%. Grade 3 or higher non-hematological toxicity included stomatitis and peripheral neuropathy in one patient each. From these results, we concluded that the COP-BLAM regimen was safe for elderly patients with HD and could achieve prolongation of survival.

Aged↗

PubMed1999

Protective effect of Irsogladine on monochloramine induced gastric mucosal lesions in rats:a comparative study with rebamipide.

AIM:To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH(2)Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective a ctivity.METHODS AND RESULTS:Oral administration of NH(2)Cl-(120mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs.Both irsogladine (1mg/kg-10mg/ kg,po) and rebamipide (30mg/kg-100mg/kg, po) dose dependently prevented the development of these lesions in response to NH(2)Cl, the effect of irsogladine was significant at 3mg/kg or greater, and that of rebamipide only at 100mg/kg. The protective effect of irsogladine on NH(2)Cl induced gastric lesions was significantly reduced by N( G) nitro L arginine methyl ester (L-NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L-NAME. Topical application of NH(2)Cl-(20mM)caused a marked reduction of potential difference (PD) in exvivo stomachs. This PD reduction was not affected by mucosal application of irso-gladine, but significantly prevented by rebamipide. The mucosal exposure to NH(4)OH (120mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH(4)OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L-NAME sensitive manner.CONCLUSION:These results suggest that (1)NH(2)Cl gen-erated either exogenously or endogenously damages the gastric mucosa, (2)both irsogladine and rebamipide protect the stomach against injury caused by NH(2)Cl,and (3)the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.

Journal Article↗

PubMed1999

[A case of medial medullary syndrome detected by diffusion-weighted magnetic resonance imaging].

We report an 84-year-old woman with medial medullary syndrome diagnosed by diffusion-weighted magnetic resonance imaging (MRI). She was admitted because of left hemiparesis and hypesthesia. T2-weighted and diffusion-weighted MRI showed a high signal lesion at the right medial medulla oblongata 10 days after the onset. It is well known that diffusion-weighted MRI is useful for detecting supratentrial cerebral ischemic lesions in the extremely acute stage. However, to our knowledge, there have been only a few reports of diffusion-weighted MRI in patients with ischemic stroke of the medulla oblongata. Normal nerve fibers in the direction perpendicular to the motion-probing gradient (MPG) shows a high signal by diffusion-weighted MRI (anisotropy of apparent diffusion cofficient [ADC]). Normal nerve fibers in the pyramidal tract of medulla oblongata also shows a high signal when the MPG pulse is applied in the x and y directions. We solved this problem by using isotropic diffusion-weighted imaging and were able to detect ischemic lesion of medial medullary infarction in the acute phase.

Aged↗