Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 775 records · Page 43Linked to original sources

PubMedDate not supplied

Acute effects of irradiation on middle ear mucosa.

Single field, fixed irradiation of bilateral tympanic cavities using 200-kV x-rays was administered to five guinea pigs. The irradiation dose was 30 Gy. They were killed immediately after irradiation, and bilateral middle ear mucosa was examined for ciliary activity and epithelial structure. Significant deterioration of the ciliary activity in the middle ear mucosa was observed, proximal as well as distal to the eustachian tube. Electron microscopy showed various changes in the irradiated middle ear mucosa. The most conspicuous findings were hyperreactivity in secretion, vacuolation of ciliated cells, and stomal edema.

Animals↗

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Effects of bacterial endotoxin on ciliary activity in the tubotympanum.

The discovery of endotoxin in effusion of otitis media with effusion (OME) has suggested the possibility that bacterial endotoxin may be involved in the pathogenesis and development of OME. In this study, we investigated the direct effects of lipopolysaccharide (LPS), possessing the major part of endotoxin activity, on the ciliary activity in the tubotympanum. The study shows that LPS deteriorates ciliary activity in a dose-response fashion and that even low levels can, with extended exposure, cause dysfunction of cilia. It can be postulated that endotoxin in middle ear effusions aggravates the condition of mucociliary dysfunction thus leading to chronic OME.

Animals↗

PubMedDate not supplied

Functional disorder of eustachian tube in experimental otitis media with effusion following inoculation of bacterial endotoxin.

A 10-micrograms/mL solution of lipopolysaccharide derived from Klebsiella pneumoniae was inoculated into the middle ears of guinea pigs. The animals were killed painlessly on the first, third, or seventh day after inoculation, and the mucosal samples from the bony portion of the eustachian tube were examined for ciliary activity and epithelial morphology. On the first and third days, when middle ear effusions were present, deterioration of ciliary activity and morphologic changes in the mucociliary system were observed. On the seventh day, when middle ear effusions were absent, the ciliary activity had recovered to normal. Our data show that endotoxin extracted from K pneumoniae can produce otitis media with effusion and that dysfunction of cilia caused by endotoxin is a factor responsible for the manifestation of otitis media.

Animals↗

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Corneal epithelial deficiency induced by the use of beta-blocker eye drops.

Two studies were conducted to check the effects of beta-blocker eye drops, 2% carteolol (Mikelan) and 0.5% timolol (Timoptol), on regeneration of corneal epithelium in rabbit eyes. For the short-term study, epithelial deficiency was artificially induced in the cornea of albino rabbits. One of the beta-blocker eye drops or 0.005% benzalkonium chloride was applied in the right eye and physiological saline solution was applied to the left eye four times a day, and wound healing rate was calculated. Two weeks later, images of the surface epithelium were analyzed by scanning electron microscopy and proliferative capacity was studied, using proliferating cell nuclear antigen as a marker. The long-term study was conducted similarly except that the eye drops were applied twice a day and epithelial deficiency was re-induced every two weeks. In the short-term study, epithelial wound healing rate was slowed in beta-blocker groups. Significant differences were detected between the Mikelan and Timoptol groups, and the benzalkonium and physiological saline groups. The beta-blocker groups had severe epithelial cell desquamation, as well as detachment. In the long-term study, the Mikelan group had significantly delayed wound healing at first induction, the benzalkonium group showed delay up to the third induction and the Timoptol group up to the fifth induction. These studies indicate that beta-blocker eye drops delay corneal epithelial wound healing and supported the concept that corneal epithelial deficiency occurs clinically after the long-term administration of beta-blocker eye drops.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Comparative study of incadronate and elcatonin in patients with malignancy-associated hypercalcaemia.

The clinical usefulness of incadronate was compared with elcatonin in 26 patients with malignancy-associated hypercalcaemia. Data from 21 and 24 patients could be used to assess efficacy and safety, respectively. Eleven patients were given a single 10-mg intravenous infusion of incadronate and 10 received twice-daily intramuscular injections of 40 IU of elcatonin for 7 consecutive days. After treatment, corrected serum calcium levels decreased significantly in both groups. The anti-hypercalcaemic effect of elcatonin was characterized by its rapid onset, with serum calcium levels reduced 1 day after administration. In contrast, the anti-hypercalcaemic effect of incadronate was more sustained but only became apparent a few days after infusion. Evaluation of symptoms revealed significantly greater improvement rates in the incadronate group compared with the elcatonin group. Adverse drug reactions were observed in three patients in the incadronate group, i.e. mild and transient fever in two cases and exacerbation of disturbance of consciousness in one case. These findings suggest that incadronate produces more marked and sustained hypocalcaemic effects than elcatonin, and that co-administration of these two drugs may yield both rapid and sustained control of malignancy-associated hypercalcaemia.

Adolescent↗

PubMedDate not supplied

Mucociliary activities in fetal rabbits.

There have been many morphological investigations on the generation of respiratory epithelium. However, the mucociliary activity of fetal respiratory epithelium has never yet been discussed. In the present work, ciliary activity and mucociliary function in the nose and the trachea of fetal rabbits were studied and, moreover, their respiratory epithelial cells were observed by scanning and transmission electron microscopy. Ciliary activity as noted on the 26th day of fetal life (day 26) for the first time in both of the nasal and the tracheal region and this activity was already equivalent to that in adult rabbits. Mucociliary transport function in either region was first noted on day 27. A quantitative as well as a qualitative immaturity of the respiratory epithelium was recognized on the last day of observation (day 29). The quantitative immaturity is characterized by 1) the ratio of ciliated to non-ciliated cells being lower than in the adult epithelium, 2) each ciliated cell possessing about three-fifths as many cilia as those of a full-grown cell, and 3) some cilia being smaller than full-grown ones and the qualitative immaturity by the directional disorder of the basal foot. No differences were observed between a cilium on day 25 or earlier, another on day 26 or later, and a full-grown cilium. It is suggested that cilia of the respiratory epithelium are morphologically prepared for motion and are activated on day 26 by changes in their surroundings, and that the poorer mucociliary transport in fetuses despite an almost normal ciliary beating is due in fairly large part to their qualitative immaturity (directional disorder of the basal foot).

Animals↗

PubMedDate not supplied

Effects of bacterial endotoxin on the ciliary activity in the in vitro middle ear mucosa.

In the present study, we have examined the hitherto unknown effects of long-term exposure to lipopolysaccharide (LPS), possessing the major parts of biological activity of endotoxin, on ciliary activity in the middle ear. Our results show that LPS can affect the ciliary activity in a dose-response fashion: 1) LPS does not impair the ciliary activity up to 168 h if the concentration is 1 ng/ml or less; 2) 10 ng/ml of LPS does not impair ciliary activity in the middle ear close to the tympanic orifice up to 168 h, but can cause reduced activity distal to the orifice after extended exposure (more than 96 h); 3) 100 ng/ml or more of LPS can cause dysfunction of cilia in the tympanic cavity, and in particular 1 microgram/ml or more of LPS can quickly disable the ciliary activity in the middle ear distal to the orifice.

Animals↗

PubMedDate not supplied

Effect of formalin-fixed Hemophilus influenzae and Streptococcus pneumoniae on dye transport by the chinchilla eustachian tube.

An in situ method for measuring the ability of the middle ear and eustachian tube ciliated epithelium to transport dye to the nasopharynx was used to assess the role endotoxin-containing killed bacteria have on the development of otitis media with effusion. In addition, electron microscopy was used to monitor histological changes induced by exposure to these organisms and the ability of the mucosa to recover. The results indicated that exposure to a killed gram-negative but not a gram-positive otitis media pathogen leads to early production of middle ear fluid, evidence of capillary leakage and significant slowing of mucociliary transport. The damage was, however, reversible with the epithelium returning to normal both functionally and histologically within 7 days of exposure.

Animals↗

PubMedDate not supplied

Structural organization of the outer hair cell wall.

The lateral wall of the mammalian outer hair cell has specialized structures composed of "subplasma lamina" and "micropillars." These structures anchor the subsurface cisternae to the inner leaflet of the cell membrane. The micropillars are arranged in parallel arrays encircling the entire inner side of the outer hair cell. The subplasma lamina appears sheet-like with rows of indentations and ridges in parallel arrays or in grid patterns among the specimens prepared for scanning electron microscopy. It is interpreted that these indentations are formed by the loss of the micropillars due to the osmium digestion. It is suggested that the subplasma lamina and micropillars may provide a rigid structure of the cylindrical shape and also may be involved in the motile activity of the outer hair cell.

Animals↗

PubMedDate not supplied

Fibronectin appears at the site of corneal stromal wound in rabbits.

Fibronectin (FN) is present both in plasma and in extracellular matrix, and is postulated to be involved in wound healing. The appearance of FN was investigated in the wounded rabbit cornea after corneal stroma was injured with a sharp knife or after lamellar keratoplasty was performed. An indirect immunofluorescence technique was employed to detect the presence of FN. Normal, unwounded rabbit cornea showed an intensive fluorescence at Descemet's membrane. Strong specific fluorescence was observed at the edge of a stromal wound and beneath the sliding epithelial cells after non-perforating incisions. These could be detected as early as 3 hours after injury. The fluorescence became the strongest at 6 hours, and and then gradually decreased in its intensity, disappearing by about 7 days when epithelial cells entirely filled the stromal wound. In case of lamellar keratoplasty, FN was detected at the interface of the graft and the recipient cornea. These results suggest that FN plays an important role in the stromal wound healing.

Animals↗

PubMedDate not supplied

Phase II dose escalation: a novel approach to balancing efficacy and toxicity of anticancer agents. Japanese Docetaxel Ovarian Cancer Study Group.

BACKGROUND: Small patient numbers in phase I trials may result in a safe but ineffective dose being recommended for phase II trials. A phase II dose escalation study may identify a dose that is both safe and effective. The Japanese phase I recommended dose of 60 mg/m2 of docetaxel (Taxotere) had been ineffective in phase II trials in ovarian carcinoma. PATIENTS AND METHODS: Patients previously treated with one platinum-based regimen for ovarian cancer received docetaxel (Taxotere) every 3 weeks. The first dose tested was 70 mg/m2. If none of the first 5 evaluable patients responded, the dose was increased. If at least one patient responded, 10 more patients were enrolled. Also, if fewer than 3 of these first 15 evaluable patients responded, the dose was increased. If at least 3 patients responded, another 15 patients were scheduled to be enrolled to confirm efficacy. Unacceptable toxicity in 4 of 5, or 10 of 15 patients would stop escalation. RESULTS: Dose escalation from 70 mg/m2 was not required because responses were noted with acceptable toxicity levels. Overall response in 25 evaluable patients treated at 70 mg/m2 was 24.0% (95% CI = 9.4-45.1%). CONCLUSION: Docetaxel 70 mg/m2 without premedication was identified as a safe and effective dose. Further testing of the phase II dose escalation design is worthwhile.

Adolescent↗

PubMedDate not supplied

Cell cycle inhibitory protein p27 in esophageal squamous cell carcinoma.

BACKGROUND: p27 protein is one of the cdk inhibitors which regulates the progression from G1 to S phase of the cell cycle. Reduced expression of p27 protein has been reported to be correlated with poor clinical outcome in patients with various cancers. MATERIALS AND METHODS: We performed immunohistochemistry of both p27 and Ki67 in 136 cases of resected human esophageal squamous cell carcinoma, and evaluated the association between p27 immunoreactivity and clinicopathological features including clinical outcome in these patients. We also examined the correlation between labeling index or the percentage of positive tumor cells for p27 and Ki67 in serial tissue sections in these cases. RESULTS: Cases with invasion of the muscularis propria or adventitia had significantly (p < 0.05) higher p27 LI (65.0 +/- 23.7) than those with invasion limited to mucosa or submucosa and those with carcinoma in situ (58.9 +/- 18.3). There were no significant correlations between p27 and other clinicopathological factors such as sex, age, tumor size, differentiation type, nodal status and histological stage. The cases with p27 LI below 40% tended to have a worse prognosis than those with p27 LI above 40%. There was no significant correlation between Ki67 and p27 LIs. CONCLUSIONS: Reduced expression of p27 may be correlated with the biological behavior of esophageal squamous cell carcinoma and may play an important role in the early stages of cancer.

Adult↗

PubMedDate not supplied

Topoisomerase II alpha expression in esophageal squamous cell carcinoma.

BACKGROUND: DNA topoisomerase II alpha (topo II alpha) is associated with active cell proliferation of mammalian cells. Topo II alpha overexpression has been reported in a number of human malignancies and is considered to be related to their biological behaviors. MATERIALS AND METHODS: We examined the expression of topo II alpha immunohistochemically in 136 cases of human esophageal squamous cell carcinoma, 10 foci of squamous dysplasia and 10 non-pathologic squamous epithelium. We calculated the labeling index (LI) or the percentage of immunopositive cells for Topo II alpha and Ki67, and Topo II alpha LI/Ki67 LI (T/K ratio). These findings were then correlated with clinicopathological features of the patients including their clinical outcome. RESULTS: Both topo II alpha and Ki67 immunoreactivity were detected in the nuclei. A significant positive correlation was obtained between Topo II alpha and Ki67 LIs in all the specimens examined. Topo II alpha LI and T/K ratio were 24.5 +/- 8.0% and 1.04 +/- 0.64 for carcinoma, 19.1 +/- 15.2% and 0.68 +/- 0.29 for dysplasia and 14.0 +/- 14.1% and 0.55 +/- 0.17 for non-pathologic epithelium, respectively. Topo II alpha LI and T/K ratio in carcinoma cases were significantly higher than those of normal epithelium. Topo II alpha LI alone did not correlate with any of clinicopathological parameters examined but among carcinoma cases, cases with lymph nodes metastasis or higher histological stages had significantly higher T/K ratio than those without lymph node metastasis or lower histological stages. In addition, carcinoma cases with T/K ratio of greater than 0.8 demonstrated significantly worse prognosis than those with T/K ratio of smaller than 0.8. CONCLUSIONS: The relative overexpression of topo II alpha as compared with Ki67, i.e., increased T/K ratio was detected in esophageal squamous cell carcinoma and is considered to represent a dysregulation or qualitative alteration in topo II alpha, possibly associated with malignances, as reported in other human cancers. In addition, topo II alpha overexpression may also be correlated with the aggressive biological behavior of the patients with esophageal squamous cell carcinoma.

Adult↗

PubMedDate not supplied

Immunohistochemical study of basaloid squamous cell carcinoma, adenoid cystic and mucoepidermoid carcinoma in the upper aerodigestive tract.

Non-squamous cell carcinoma is a rare but distinct neoplasm of the upper aerodigestive tract. Among these carcinomas, basaloid-squamous cell carcinoma (BSCC) has frequently been confused with adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma of the upper aerodigestive tract. In this study, we examined immunohistochemically the expression of differentiation-related substances, including cytokeratin (CK) subtypes, p53 and p27, and cell adhesion-related molecules E-cadherin and alpha-catenin to clarify the biological features of these neoplasms. We studied seven cases of BSCC of the oesophagus, five cases of ACC and seven cases of mucoepidermoid carcinoma. Squamous cell carcinoma and adenocarcinoma of the oesophagus and trachea were also studied for comparison. Among the cytokeratin subtypes examined, CK14, CK17 and CK19 immunoreactivity was detected in BSCC. ACC and mucoepidermoid carcinoma were immunopositive for CK8, CK14 and CK17 and for CK8, CK14, CK17 and CK19, respectively. These findings suggest that CK subtypes, especially CK8, CK14 and CK17, are useful in differentiating these malignancies. BSCC was more frequently associated with decreased E-cadherin and alpha-catenin immunoreactivity than ACC and mucoepidermoid carcinoma. Nuclear p53 immunoreactivity was detected more frequently in BSCC (5 out of 7) than in ACC (2 out of 5) and mucoepidermoid carcinoma (4 out of 7). There were no significant differences in p27 immunoreactivity among these carcinomas. Carcinoembryonic antigen (CEA) immunoreactivity was detected in mucoepidermoid carcinoma (2 out of 7), SCC (8 out of 11) and adenocarcinoma (9 out of 9), but it was not detected in BSCC (7) or ACC (5). Carbohydrate antigen 19-9 (CA19-9) immunoreactivity was detected only in mucoepidermoid carcinoma (4 out of 7) and adenocarcinoma, but not in BSCC, ACC, or SCC. These findings indicate that BSCC, ACC and mucoepidermoid carcinoma are distinct neoplasms arising in the upper aerodigestive tract. In addition, decreased expression of E-cadherin and alpha-catenin proteins and increased p53 expression in BSCC may be correlated with aggressive behaviour.

Adenocarcinoma↗

PubMedDate not supplied

Significance of tumor associated tissue eosinophilia and other inflammatory cell infiltrate in early esophageal squamous cell carcinoma.

Tumor associated inflammatory cell infiltration plays an important role in the biological behavior of cancer as one of the carcinoma-stromal interactions. In this study, we characterized inflammatory cell infiltration on esophageal squamous cell carcinoma (SqCC) and correlated the findings with various clinicopathological factors, including clinical outcome of the patients, in order to study its biological significance. We examined 35 cases of surgically resected early esophageal SqCC or carcinoma with invasion limited to the submucosal layer. We evaluated the abundance of CD4+ T-cell, CD8+ T-cell, B-cell, plasma cell, CD68+ macrophage, neutrophil and eosinophil in the stroma adjacent to the tumor and correlated these findings with clinicopathological factors. The cases without LN metastasis had a significantly larger number of tumor associated eosinophils than those with LN metastasis. Primary lesions in cases without LN metastasis tended to demonstrate more CD68+ macrophage infiltration than those with LN metastasis, but the difference did not reach statistical significance. In addition, the cases with more than 50 eosinophils and macrophages per 10 high power field in the primary lesion demonstrated a significantly smaller incidence of LN metastasis than those with less than 50 eosinophils and macrophages per 10 high power field. Thus tumor associated tissue eosinophila, also known as TATE, is considered to be involved in the biological behaviour of early esophageal SqCC, especially in their metastatic potential.

Aged↗

PubMedDate not supplied

An individual patient data meta-analysis of long supported adjuvant chemotherapy with oral carmofur in patients with curatively resected colorectal cancer.

To reappraise the benefits of the long supported chemotherapy with carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for carmofur; and a highly significant advantage for carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.

Administration, Oral↗

PubMedDate not supplied

Meta-analysis of adjuvant immunochemotherapy using OK-432 in patients with resected non-small-cell lung cancer.

The benefits of immunochemotherapy with a penicillin-treated, lyophilized preparation of Streptococcus pyogenes, OK-432 (Picibanil), were reassessed in patients with resected non-small-cell lung cancer through a meta-analysis based on data from 1,520 patients enrolled in 11 randomized clinical trials. All 11 trials were started before 1991, and the subjects had been followed up for at least 5 years after surgery and randomization. In these trials, standard chemotherapy was compared with the same therapy plus OK-432. The endpoint of interest was overall survival, and analysis was based on intent-to-treat population without patient exclusion. Data were analyzed using the Mantel-Haenszel method. The 5-year survival rate for all eligible patients in the 11 trials was 51.2% in the immunochemotherapy group versus 43.7% in the chemotherapy group. The odds ratio (OR) for overall survival was 0.70 (95% CI = 0.56-0.87, p = 0.0010). Analysis of four trials in which central randomization was performed also reconfirmed a significantly longer survival time for the immunochemotherapy group (OR = 0.66, 95% CI = 0.44-1.00, p = 0.049). Based on these results of meta-analysis, it is postulated that postoperative adjuvant immunochemotherapy using OK-432 might improve the survival of patients after resection of non-small-cell lung cancer.

Antineoplastic Agents↗

PubMedDate not supplied

Alteration of X and Y chromosomes in human esophageal squamous cell carcinoma.

The incidence of human esophageal squamous cell carcinoma in males is well-known to be higher than in females and its biological action in male patients is generally much more aggressive than that of the female. Recently, aberrations and/or other abnormalities of the sex chromosomes, especially the Y chromosome, have been postulated to be involved in some of the differences in the incidence and/or biological action of human malignancies between male and female patients. Therefore, in this study, we examined abnormalities of the sex chromosomes in cell smears obtained from 30 male patients diagnosed with esophageal squamous cell carcinoma. In addition, TE series cell lines, derived from esophageal squamous cell carcinomas, were studied for sex chromosome abnormalities by utilizing a simultaneous double color fluorescent in situ hybridization (FISH) and these findings were correlated with various clinicopathological parameters in order to examine its likely biological significance. In esophageal squamous cell carcinoma, Y chromosome loss was detected in all cases studied (1.6-86.9%, mean 22.98 +/- 22.04%), but the loss of the X chromosome was encountered in only 6 of the cases (7.1-40.6%, mean 15.90 +/- 12.46%). There was no significant association between the rate of Y chromosome loss in carcinoma cells and any of the clinicopathological parameters examined including age and stage of the cancer. Loss of the Y chromosome was observed in only two cases of adjacent non-pathological esophageal squamous cell epithelium. Among the TE series examined, the cell lines derived from male patients demonstrated loss of the Y chromosome in all cell lines (1.4-92.9%, mean 44.92 +/- 42.55%), but the great majority of cell lines derived from female patients were associated with the karyotype of XX. These results indicated that the loss of the Y chromosome is associated with the malignant phenotype in human esophageal squamous epithelium, but possibly not with biological behavior. These results also suggested that at least one X chromosome is indispensable for the survival of esophageal squamous cell carcinoma.

Aged↗