Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 163 records · Page 9Linked to original sources

PubMed1997

Feasibility of the transparent cap-fitted colonoscope for screening and mucosal resection.

PURPOSE: A transparent plastic cap of 17 mm in outer diameter, 15 mm in inner diameter, and 10 mm in length can be easily attached to the tip of a colonoscope. By using the cap, a better view of the lesions hiding at the opposite side of the fold can be obtained. When a flat colonic lesion is found, a submucosal injection of saline solution is performed, the target mucosa is sucked inside the cap, snared under a full endoscopic suction, and resected by an electrical current. This procedure is called endoscopic mucosal resection using transparent cap-fitted endoscope (EMRC). Feasibility of the cap-fitted colonoscope for screening colonoscopic examination and mucosal resection was evaluated. MATERIALS AND METHODS: One hundred forty patients were randomly allocated for screening with a normal colonoscope (NCF) or that with the cap-fitted colonoscope (CCF). Average time for insertion up to the cecum, patients' discomfort during insertion expressed in 4 degrees, and average number of lesions found in one patient were compared. Thirty lesions randomly allocated for mucosal resection with conventional strip biopsy or EMRC were also evaluated. RESULTS: Time consumed for insertion up to the cecum with the CCF (12.4 +/- 6.6 minutes) was the same as that with the NCF (12.3 +/- 5.2 minutes), and there was no significant difference in patients' discomfort; however, the average number of lesions found in one patient was larger when using the CCF (0.86 +/- 0.96) than when using the NCF (0.58 +/- 0.81). For mucosal resection, 40 flat or wide-based lesions including 6 mucosal carcinomas were resected with EMRC. We experienced only one pinhole perforation of the ascending colon by heat damage, which was treated successfully by surgery. There was no other major complication or recurrence. CONCLUSION: The cap-fitted endoscope was equal in maneuverability, was excellent in sensitivity in comparison with the regular colonoscope, and was thought to be feasible both in screening and mucosal resection.

Aged↗

PubMed1997

Serotonin receptor mRNA expression in the hypoglossal motor nucleus.

Brainstem serotonin (5-HT)-containing cells are remarkable for their widespread axonal projections and having their highest activity during wakefulness and lowest during rapid eye movement sleep. One important site of action of 5-HT is on upper airway motoneurons. However, which of the 14 known 5-HT receptors mediate the effects is uncertain. We used the reverse transcriptase/polymerase chain reaction to detect mRNA for six distinct 5-HT receptors (1A, 1B, 2A, 2C, 3 and 7) in 50 nl micro-punches collected from the hypoglossal (XII) motor nucleus and, for comparison, from the viscerosensory nucleus of the solitary tract (NTS) in adult rats. The relative abundance of the distinct mRNAs was characterized by the minimal number of amplification cycles (25-40) necessary to detect a given mRNA. In the XII nucleus, mRNA for type 1B, 2A and 2C receptors was detectable after 29-31 cycles, detection of type 3 and 7 receptor mRNA required 33-35 cycles; and type 1A receptor mRNA was not detected. In the NTS, detection of mRNA for type 1B, 2C and 7 receptors required 31-33 cycles; type 1A receptor mRNA required 39 cycles; and type 2A receptor mRNA was not detected. The data from the XII nucleus demonstrate that not only the previously recognized type 1B, 2A and 2C receptors, but also type 3 and 7 receptors have the potential to mediate serotonergic effects in XII motoneurons.

Animals↗

PubMed1997

Differential sensitivity of laryngeal and pharyngeal motoneurons to iontophoretic application of serotonin.

Serotonergic neurons decrease their activity during sleep, especially rapid eye movement sleep, thereby reducing their facilitatory effect on upper airway motoneurons. The magnitude of teh sleep-related loss of tone varies among upper airway muscles (e.g., pharyngeal dilator motoneurons are more suppressed than laryngeal motoneurons). We hypothesized that these differences may be related to the sensitivity of different groups of upper airway motoneurons to serotonin. Experiments were done on decerebrate, vagotomized, paralysed and artificially-ventilated cats. Hypoglossal and laryngeal motoneurons were recorded extracellularly using five-barrel pipettes filled with: serotonin, glutamate and methysergide (serotonergic antagonist) for iontophoresis, and NaCl for recording and current balancing. All but two of the 65 hypoglossal motoneurons (45 inspiratory, 10 expiratory, 10 tonic) and 27 out of 32 laryngeal motoneurons (14 inspiratory, 18 expiratory) were excited by serotonin, and the excitation was abolished by methysergide. To compare the magnitude of the excitatory effect among distinct motoneuronal groups, we applied small ejection currents in a standardized manner (+15 nA for 3 min; 10 mM serotonin in 150 NaCl) onto spontaneously active motoneurons (13 inspiratory hypoglossal, 11 inspiratory laryngeal and 11 expiratory laryngeal). Serotonin increased the number of spikes per respiratory burst of inspiratory hypoglossal motoneurons from 19 +/- 4.0 (S.E.M.) to 35 +/- 4.8, of inspiratory laryngeal motoneurons from 44 +/- 8.3 to 55 +/- 8.8, and of expiratory laryngeal motoneurons from 23 +/- 4.8 to 33 +/- 6.2. The relative increases in activity (to 220% +/- 24, 147% +/- 23 and 148% +/- 9 of control, respectively) were significantly higher in hypoglossal than in laryngeal motoneurons. In addition, the excitatory effect developed significantly faster in hypoglossal than in laryngeal motoneurons. Methysergide reduced the spontaneous activity of about half the hypoglossal and laryngeal motoneurons to 66% +/- 5 of control. Thus, the sensitivity to the excitatory effects of serotonin varies among different pools of upper airway motoneurons. These differences correlate with the pattern of airway muscle hypotonia seen during sleep.

Action Potentials↗

PubMed1997

Effects of growth factors on acid-induced damage to rat gastric epithelial cells.

We previously established a model of cell damage induced by an acidified medium in the rat gastric epithelial cell line RGM1. Treatment of the cells with epidermal growth factor (EGF, 1-10 ng/ml) for 4 h prevented acid-induced cell damage in a concentration-dependent manner. In contrast, basic fibroblast growth factor (1-10 ng/ml) and platelet-derived growth factor BB (1-10 ng/ml) had no effect on cell damage. EGF did not affect DNA synthesis by the cells for 4 h. Pretreatment of the cells with cycloheximide (10 micrograms/ml) for 1.5 h before EGF treatment significantly attenuated the cytoprotective effect of EGF by > 50%. Replacement of Na+ with K+ in the acidified medium totally abolished the effect of EGF. Co-incubation with amiloride (1 mM) had no influence on the protective effect of EGF. These results indicate that the cytoprotective effect of EGF appears to involve both the activation of amiloride-resistant Na+/H+ exchangers and the synthesis of a new protein related to Na+/H+ exchangers.

Amiloride↗

PubMed1997

Hypothesis--origin of the parietal cell: microorganism?

Parietal cells, which exist in the stomach and in Meckel's diverticulum of the ileum, secrete hydrochloric acid by means of H+,K(+)-ATPase (alpha- and beta-subunits) in the human body. Although parietal cells are generated from progenitor cells (stem cells), their lifespan (approximately 150-200 days) is distinctly longer than that of surface epithelial cells (4 days), which are also derived from stem cells. Microorganisms, including bacteria (both aerobic and anaerobic), are able to pump H+ out by means of H(+)-ATPase. Of interest is that 19% of the human H+,K(+)-ATPase (alpha-subunit) comprises amino acid residues identical to those of the H(+)-ATPase found in Neurospora crassa. In addition, the amino acid sequence in the ATP binding sites of animal Na+,K(+)-ATPase and yeast H(+)-ATPase with phosphorylated intermediates is highly conserved. These data appear to indicate that the parietal cell might have originated from a microorganism that was parabiosed in a separate origin, having digestive organs, that was later incorporated into a stem cell. Thereafter, the gene encoding H+,K(+)-ATPase, or those encoding GATA DNA binding proteins (transcriptional regulators of the gastric H+,K(+)-ATPase gene), or both were translocated into the nuclei, most probably with the aid of a virus and/or a transposon under unusual circumstances. This type of gene translocation most probably occurred during the Cambrian era when Prochordata and Chordata, which have no parietal cells, were abundant. This suggests that in the process of evolution, the stem cells in the digestive organs of the Cordata might have differentiated into two cell types, i.e., surface epithelial cells and parietal cells, before the appearance of fish (which possess parietal cells with H+,K(+)-ATPase).

Animals↗

PubMed1997

Mechanisms of growth inhibition of human lung cancer cell line, PC-9, by tea polyphenols.

(-)-Epigallocatechin gallate (EGCG), the main constituent of green tea, and green tea extract show growth inhibition of various cancer cell lines, such as lung, mammary, and stomach. We studied how tea polyphenols induce growth inhibition of cancer cells. Since green tea extract contains various tea polyphenols, such as EGCG, (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC), the inhibitory potential of each tea polyphenol on the growth of a human lung cancer cell line, PC-9 cells, was first examined. EGC and ECG inhibited the growth of PC-9 cells as potently as did EGCG, but EC did not show significant growth inhibition. The mechanism of growth inhibition by EGCG was studied in relation to cell cycle regulation. Flow cytometric analysis revealed that treatment with 50 microM and 100 microM EGCG increased the percentages of cells in the G2-M phase from 13.8% to 15.6% and 24.1%, respectively. The DNA histogram after treatment with 100 microM EGCG was similar to that after treatment with genistein, suggesting that EGCG induces G2-M arrest in PC-9 cells. Moreover, we found by microautoradiography that [3H]EGCG was incorporated into the cytosol, as well as the nuclei. These results provide new insights into the mechanisms of action of EGCG and green tea extract as cancer-preventive agents in humans.

Antineoplastic Agents↗

PubMed1997

Characterization of a novel cell damage model induced by acid and pepsin using rat gastric epithelial cells: protective effect of sucralfate.

We have established a new model for rat gastric epithelial cell (RGM1) damage caused by both acid and pepsin. Exposure of RGM1 to an acidified medium (pH 3.5-5.0) for 10-50 min decreased cell viability in a time- and pH-dependent manner. Pepsin (0.5-1.0 mg/mL) at pH 4.5 potentiated cell damage in a concentration-dependent manner. Based on these results, two types of cell damage models caused by incubation of cells at pH 4.0 and with pepsin (0.75 mg/mL) at pH 4.5 for 30 min, respectively, were established. The intracellular pH (pHi) gradually decreased with a decrease in medium pH and an increase in exposure time. At pH < or = 4.0, pHi reached approximately pH 6.3. Pepsin at pH 4.5 caused a further reduction in pHi compared with the acidified medium alone. Pepsin pre-incubated with pepstatin did not induce any cell damage. Pretreatment with sucralfate (0.1-3 mg/ mL) for 2 h significantly prevented cell damage caused at both pH 4.0 and with pepsin at pH 4.5 in a concentration-dependent manner. Sucralfate (3 mg/mL) significantly prevented the reduction in pHi at pH 4.0 or with pepsin at pH 4.5. 16,16-Dimethyl prostaglandin E2 (30 micrograms/mL) had no effect on either cell damage or pHi. These cell damage models involving RGM1 are useful for studying the mechanism underlying cell damage and for the screening of cytoprotective drugs.

Animals↗

PubMed1997

Cytoprotective effect of epidermal growth factor on acid- and pepsin-induced damage to rat gastric epithelial cells: roles of Na+/H+ exchangers.

We have previously established a cell damage model, with damage induced by either acid or pepsin treatment for 30 min, involving a rat gastric epithelial cell line (RGM1). In the present study, pretreatment of cells with epidermal growth factor (EGF; 0.1-10 ng/mL) or sucralfate (0.1-3 mg/mL) for 4 h prevented such cell damage in a concentration-dependent manner. Protection of cells by these drugs was not affected by pretreatment with indomethacin (10(-5) mol/L) for 4 h. Removal of Na+, but not Ca2+, from the acidified medium totally abolished the inhibitory effect of EGF, but not that of sucralfate. Genistein (a tyrosine kinase inhibitor) apparently reduced the inhibitory effect of EGF. DNA synthesis by RGM1 cells did not increase when cells were incubated with EGF for 4 h. We conclude that both EGF and sucralfate protect RGM1 cells from acid- and pepsin-induced damage and that the mechanism of protection by EGF against acid-induced damage seems to be via activation of Na+/H+ exchangers.

Acids↗

PubMed1997

Papillary eccrine adenoma: immunohistochemical studies of keratin expression.

Despite various studies, there are serious disagreements about the cellular differentiation of papillary eccrine adenoma. In the present study, 2 specimens of papillary eccrine adenoma were analyzed by immunohistochemical techniques, using a panel of monoclonal antibodies against keratins, to elucidate its differentiation. Histopathologically, the tumor was composed of multiple tubular structures lined by two or more layers of epithelial cells. The luminal cells of the tubules were flattened or cuboidal. The former were noted in large dilated tubules. The latter were usually observed in small-to-moderate-sized tubules, and formed intraluminal papillary projections in some tubules. Immunohistochemically, there were two kinds of cuboidal cells in the luminal layers of the tubules. Most of the large dilated tubules and some of the small-to-moderate-sized tubules expressed immunophenotypes similar to those of the eccrine dermal duct. The other tubular structures, including the small tubules resembling those of syringoma, expressed immunophenotypes similar to those of the transitional portions between the dermal ducts and the secretory segments of eccrine glands. From the above comparative studies, papillary eccrine adenoma is considered to differentiate towards the dermal duct and the transitional portions between the dermal ducts and the secretory segments of eccrine glands.

Adenoma, Sweat Gland↗

PubMed1997

Leminoprazole protects cultured gastric mucosal cells against damage caused by ethanol, indometacin and taurocholate.

We examined whether or not leminoprazole (an acid pump inhibitor) protects cultured rabbit gastric mucosal cells against various forms of cell damage. Exposure of mucosal cells to ethanol, indometacin or taurocholate for 1 h caused a reduction in their viability. Pretreatment of the cells with leminoprazole for 2 h concentration-dependently and significantly prevented the viability loss induced by each noxious agent, although the drug alone did not affect cell viability. Cytoprotection by leminoprazole was expressed after a 2-hour lag period. The effects of leminoprazole were potently inhibited by cycloheximide and actinomycin D. These results indicate that leminoprazole directly acts on gastric mucosal cells, making the cells resistant to damage, and that its cytoprotection might be mediated through de novo synthesized proteins.

Animals↗

PubMed1997

Lack of ventilatory threshold in patients with chronic obstructive pulmonary disease.

We investigated whether the ventilatory threshold (VET) could be detected in 25 patients with severe chronic obstructive pulmonary disease (COPD). Exercise on a treadmill was performed until symptom-limited maximum oxygen uptake (VO2SL) was obtained. VET was absent in 14 patients (56%, VET(-) group) and present in the others (44%, VET(+) group). Basal pulmonary functions and dyspnea index (VE,SL/MVV) were not different between the two groups. Endurance time and exercise tolerance (VO2SL/bw) were significantly less in VET(-) than in VET(+). In the former group, PaO2 and pH at maximal exercise decreased and PaCO2 increased significantly, but HCO3- did not change compared with the corresponding values before exercise. In the latter group, PaCO2 at maximal exercise increased significantly, and pH and HCO3- decreased significantly compared with the values before exercise, but PaO2 did not. The changes in PaO2 and PaCO2 were not different between the two groups, but changes in pH and HCO3- in VET(+) were greater than those in VET(-). These results suggest that the absence of VET in some COPD patients indicates a lower exercise capacity without producing metabolic acidosis. This may be caused by rapidly developing dyspnea.

Aged↗

PubMed1997

Cytoprotective effects of 4,6-bis(1H-pyrazol-1-yl)pyrimidine and related compounds on HCI.ethanol-induced gastric lesions in rats.

Bis(1H-pyrazol-1-yl)- and bis(1H-imidazol-1-yl)pyrimidines were synthesized and evaluated for cytoprotective effects. Among them, 4,6-bis(1H-pyrazol-1-yl)pyrimidine (3) showed a potent inhibitory effect on the HCl.ethanol-, ethanol-, and water immersion stress-induced gastric lesions in rats, and a very low acute toxicity. One of the major factors responsible for the cytoprotective effects of 3 is the increase in the bicarbonate secretion. This compound appears to be a promising cytoprotective drug for the treatment of gastric mucosal ulcers.

Animals↗

PubMed1997

Improvement of exercise performance with short-term nasal continuous positive airway pressure in patients with obstructive sleep apnea.

We examined the effects of nasal continuous positive airway pressure (CPAP) on exercise performance in patients with obstructive sleep apnea (OSA). Six patients were treated with nasal CPAP on seven successive days and underwent overnight sleep studies and multiple sleep latency test (MSLT) at the beginning and after the last day of the treatment. The subjects also performed incremental exercise testing using a bicycle ergometer followed by 0-w, 25-w, 50-w,--(3 minutes each) until maximum level. Arterial oxygen pressure, arterial carbon dioxide pressure at rest while awake, apnea/ hypopnea index, longest apnea duration, the lowest percutaneous oxygen saturation measured by a pulse oximeter and the value of MSLT were significantly improved after nasal CPAP. Moreover, maximal oxygen consumption was significantly increased from 1841 ml/min +/- 350 to 2125 ml/min +/- 351 (p < 0.05); however, other cardiorespiratory parameters did not change significantly. The improvement of exercise performance by short-term nasal CPAP treatment in OSA patients may correlate with the improvement of sleepiness.

Adult↗

PubMed1997

Diffuse alveolar hemorrhage associated with proteinase 3-specific anti-neutrophil cytoplasmic antibodies.

A 31-year-old man was referred to our hospital for the management of progressive diffuse alveolar hemorrhage associated with renal dysfunction. Leukocytoclastic vasculitis was shown by skin biopsy and crescentic glomerulonephritis was also detected, in addition to positivity for proteinase 3-specific anti-neutrophil cytoplasmic antibodies (PR3-ANCA). The patient was diagnosed as a rare case of PR3-ANCA-positive pulmonary-renal vasculitic syndrome without granulomatous lesions. There was a good response to combination therapy with steroids and cyclophosphamide.

Adult↗

PubMed1997

A prospective, randomized clinical trial of preoperative bowel preparation for elective colorectal surgery--comparison among oral, systemic, and intraoperative luminal antibacterial preparations.

During a one year and six month period, 137 patients undergoing elective colorectal surgery for carcinoma were randomly allocated to three groups. Patients in group A received oral tobramycin and metronidazole for three days prior to surgery. Patients in groups B and C received systemic antibiotic, a second generation cephem cefmetazole, every 3 hours during surgery. Patients in group C also received a luminal preparation of tobramycin during surgery. All patients received mechanical bowel preparation in the same manner. The incidence of postoperative wound sepsis was 10.9% in group A, 9.8% in group B, and 10.0% in group C. There were no significant differences in postoperative wound sepsis among the three groups. The oral antibiotic regimen induced a greater change in intestinal flora and was associated with more frequent postoperative diarrhea. Although the preoperative bowel preparation taken for patients in group A could not sufficiently reduce the intestinal bacterial count, systemic antibiotic prophylaxis was simple and cost-effective. There was no additional advantage in combining the systemic and luminal antibiotic preparations. Therefore, for elective colorectal surgery, we recommend intravenous infusion of second generation cephem cephmetazole with mechanical bowel preparation.

Administration, Oral↗

PubMed1997

[Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver].

We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.

Administration, Oral↗

PubMed1997

Characterization of antichemotactic factor extracted from the gastric mucosa of rats.

The gastric mucosa of normal rats exhibits no detectable inflammation or visible damage. We examined the effect of the gastric mucosal extract of rats on neutrophil chemotaxis and tried to purify antichemotactic factor. The chemotaxis of neutrophils was examined by the modified Boyden's method. After mucosal layer was scraped and then homogenized and centrifuged at 20,000 x g for 30 min, the supernatant was used as rat gastric mucosal extract (RGME). Prior exposure of neutrophils to the gastric mucosal extract caused a dose-dependent reduction in the neutrophil migration induced by formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) and interleukin 8 (IL-8) without affecting the cell viability. The antichemotactic factor was partially purified by lectin affinity chromatography on wheat germ lectin (WGL)-Sepharose, anion exchange chromatography on Mono-Q and gel filtration on Superose 12. The molecular weight of the antichemotactic factor was estimated to be around 60 k by gel filtration. The activity was markedly abolished by boiling for 5 min, heating at 60 degrees C for 30 min, and treatment with 1% acetic acid, 0.1 M Na2CO3 or trypsin. Furthermore, the FMLP-induced migration of neutrophils pretreated with the antichemotactic factor for 5 min followed by washing with fresh medium was inhibited, although the factor was not added to the chamber. These results suggest that the gastric mucosa of rats intrinsically generates an antichemotactic factor which might play a crucial role in maintenance of the integrity of the gastric mucosa.

Animals↗

PubMed1996

The BCL6 gene is predominantly expressed in keratinocytes at their terminal differentiation stage.

We analyzed the expression of the BCL6 gene in mouse tissues by in situ hybridization. The expression was strong in the upper layer but undetectable in the basal layer of epidermis from adult mice. When human keratinocytes were cultured with a high concentration of calcium ion, these cells stopped their proliferation and differentiated to their terminal stage. In these keratinocytes, BCL6 expression was induced after stimulation and progressively up-regulated. The kinetics was very similar to that of a cyclin dependent kinase inhibitor p21sdil/cip1/WAF1 in these cells. These results suggest that BCL6 plays a role in keratinocytes at terminal differentiation stage.

Animals↗