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Biomedical subjects

I Okayasu

Publications and source records attributed to I Okayasu.

At least 91 records · Page 5Linked to original sources
PubMed1998

Development of pyothorax-associated pleural lymphoma in relation to focal cytokinemic condition and Epstein-Barr virus infection.

We report an initial case of pyothorax-associated pleural lymphoma (PAPL) in which the level of interleukin 6 (IL-6) was remarkably high in the pleural fluid contaminated with tumor cells; at the same time Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were detected in the lymphoma cells by in situ hybridization. These findings suggest the possibility that EBV-transformed B cells proliferated in the focal cytokinemic condition caused by long-standing chronic inflammation of the pleura and give us a clue to the lymphoma genesis of PAPL.

Aged↗
PubMed1998

Magnetometric evaluation for the effect of chrysotile on alveolar macrophages.

Alveolar macrophages are thought to play an important role in fibrogenesis due to asbestos exposure. In this experiment, we evaluated the effect mainly by unique magnetometry and also by conventional methods such as lactate dehydrogenase (LDH) activity measurement and morphological observations. Alveolar macrophages obtained from Syrian golden hamsters by bronchoalveolar lavages were exposed 18 hours in vitro to Fe3O4 as an indicator for magnetometry and chrysotile for experiments. A rapid decrease of the remanent magnetic field, so called "relaxation", was observed after the cessation of an external magnetic field in macrophages phagocytizing Fe3O4 alone, while relaxation was delayed in those concurrently exposed to chrysotile. Since relaxation is thought due to the cytoskeleton-driven random rotation of phagosomes containing iron oxide particles, chrysotile is considered to interfere with the cytoskeletal function of macrophages. Release of LDH from chrysotile-exposed macrophages into the medium was recognized, but it was not significantly higher than the controls. Apoptosis was negligible in macrophages exposed to chrysotile by the DNA ladder detection, the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling method and morphological observations. Electron microscopical examinations revealed early necrotic changes in macrophages exposed to chrysotile. These findings indicate that cell magnetometry detects impaired cytoskeletal function due to in vitro exposure to chrysotile.

Animals↗
PubMed1998

[Significant correlation of telomerase activity in lung adenocarcinomas with cell differentiation and chromosome aberration].

Of a total of 21 surgically resected lung adenocarcinomas (15 men and 6 women with an average age of 59.6 yr) well, moderately and poorly differentiated types were 6, 7 and 8 cases, respectively. Telomerase activity determined by the TRAP assay was classified into four types as follows; negative = Score 0, weakly positive = 1, moderately positive = 2, strongly positive = 3. Chromosome aberrations were also classified into four groups: Score 0, 1, 2, 3 according to the number of marker chromosomes, 0, 1-5 6-15 and over 16 respectively. CT-Indices (chromosome aberration x telomerase activity) of well, moderately, and poorly differentiated types were 1, 4.3, 5.1 respectively. Thus, CT-Indices were correlated with cell differentiation in the lung adenocarcinomas (p < 0.01).

Adenocarcinoma↗
PubMed1997

Expression of bcl-2 protein in esophageal squamous cell carcinomas and its association with lymph node metastasis.

BACKGROUND: Recent studies on the role of bcl-2 in malignant tumors have suggested its prognostic significance. The goals of the current study were to determine any correlation between bcl-2 expression in esophageal squamous cell carcinoma and histopathology, lymph node metastasis, and clinical variables, and to assess its applicability as a parameter for prognosis. METHODS: Immunohistochemical staining for bcl-2 (clone 124) was performed on archival material from 105 esophageal squamous cell carcinomas. The results were compared among patient subgroups. RESULTS: bcl-2 was expressed in 58% of esophageal carcinomas, demonstrating positive correlations with a lack of keratinization and an early stage of disease. Lymph node metastasis was significantly less frequently observed in the subset of early stage carcinomas with bcl-2 staining. Univariate analysis revealed significantly longer disease free survival in patients with bcl-2 positive carcinomas than in those bcl-2 negative. bcl-2 expression did not have independent prognostic value in a multivariate survival analysis. CONCLUSIONS: bcl-2 is frequently expressed in esophageal carcinomas, and this expression is positively associated with nonkeratinization and an early stage, whereas it is negatively linked with lymph node metastasis and may indicate a favorable prognosis.

Carcinoma, Squamous Cell↗
PubMed1997

Down-regulation of bcl-2 expression is closely related to squamous differentiation and progesterone therapy in endometrial carcinomas.

To clarify whether changes in bcl-2 protein (bcl-2) expression are directly linked to differentiation, an immunohistochemical investigation was carried out on areas of squamous differentiation within 38 endometrial carcinomas (25 grade 1 and 13 grade 2 cases) as well as eight grade 1 carcinomas after progesterone therapy. Such areas of altered differentiation were subdivided into foci of squamous metaplasia (Sq-M) and morules. Expression of oestrogen and progesterone receptors (ER and PR) and cell proliferation were also examined. Immunoreactivity scores for bcl-2 in Sq-M foci were significantly lower than in the surrounding tumour regions, in line with reduced staining for ER and PR and Ki-67 labelling indices (LIs), while morule values were intermediate. After progesterone therapy, a marked decrease in bcl-2 immunoreactivity was found in the response group, along with low Ki-67 LIs and tumour cell maturation. These results indicate that in endometrial carcinoma, down-regulation of bcl-2 expression may be closely linked with squamous differentiation, in line with changes in ER and PR expression, as well as in cell proliferation. In addition, bcl-2 expression appears to be down-regulated by progesterone therapy through tumour cell maturation, indicating that bcl-2 may be a clinically useful marker of hormone therapy effects.

Biomarkers, Tumor↗
PubMed1997

Apoptosis, proliferative activity and Bcl-2 expression in Epstein-Barr-virus-positive non-Hodgkin's lymphomas.

In order to clarify the effects of Epstein-Barr virus (EBV) infection on apoptosis and proliferative activity of non-Hodgkin's lymphoma, 135 Japanese lymphoma cases were investigated for the presence of viral RNA and its correlation with bcl-2 protein (Bcl-2) expression. In addition, the role of EBV in lymphoma-genesis was also studied in terms of EBV genotyping and specific deletion in the gene for the latent membrane protein 1 (LMP-1). EBER-1 RNA in situ hybridization revealed EBV in 18 cases (13.3%), comprising 12 of 44 T cell (27.3%) and 6 of 91 B cell (6.6%) lymphomas. Type A EBV was found in all 18 cases (100%), and 17 of the 17 (100%) evaluable cases showed a 30-bp deletion within the 3' end of LMP-1. Comparison of apoptotic indices (AI), assessed by DNA nick-end labelling, and proliferative activity, estimated in terms of Ki-67 labelling and mitotic indices (KI and MI), demonstrated an overall correlation among AI, KI and MI increases in association with Bcl-2 negativity, indicating a close relation between apoptosis and proliferation. EBV-positive cases showed significantly elevated AI values, independent of Bcl-2 positivity, with no change in KI and MI. These results indicate that EBV in Japanese non-Hodgkin's lymphomas is exclusively of type A with a specific deletion in LMP-1 and that it tends to be present in T cell lymphomas. Moreover, EBV up-regulates apoptosis without any relation to Bcl-2 expression and exerts only minor effects on proliferation.

Apoptosis↗
PubMed1997

Bcl-2 is closely correlated with favorable prognostic factors and inversely associated with p53 protein accumulation in endometrial carcinomas: immunohistochemical and polymerase chain reaction/loss of heterozygosity findings.

To clarify the relation between bcl-2 protein (Bcl-2) expression and p53 alteration during progression of endometrial carcinomas (endometrioid type), 92 consecutive hysterectomy specimens were examined by immunohistochemistry. Loss of heterozygosity (LOH) for the p53 gene was also examined using the polymerase chain reaction(PCR)-LOH assay. Moderate to strong Bcl-2 immunointensity in more than 30% of cells was found in 32 (34.8%) of 92 carcinomas, with a clear link to favorable clinicopathological features, such as a high differentiation grade (P = 0.0084), an early stage (P = 0.0432) and limited invasion into the myometrium (P = 0.0084). In contrast, positive results for p53 immunohistochemistry (more than 30% positive cells) or PCR-LOH analysis were revealed in 16 (17.4%) of 92 and 18 (22.5%) of 80 tumors respectively. Although there was no apparent association between the nuclear p53 staining and the presence of LOH, the lack of correlation being observed in 23 (28.7%) of the tumors, both alterations were significantly linked with several unfavorable prognostic factors. In addition, an inverse correlation was observed between Bcl-2 expression and p53 protein accumulation (P = 0.0084). These data suggest that, in endometrial carcinomas, Bcl-2 and p53 alterations may play important roles in determining whether tumor progression from early to advanced stages will occur.

Disease Progression↗
PubMed1997

The gastric hypercellular microleiomyoma as a precursor lesion for clinical gastrointestinal stromal tumors.

Differentiation features and proliferation activity of 67 gastric microleiomyomas (microLMs) and 53 clinical gastrointestinal stromal tumors (GISTs) of the stomach were compared. The 67 microLMs were divided into two categories on the basis of cellularity: 53 hypocellular and 14 hypercellular types, and the 39 GISTs were divided into 13 low-grade and 40 high-grade lesions. Immunohistochemically, 49 hypocellular microLMs (92%) were positive for alpha-smooth muscle actin and desmin, whereas only 16 (30%) were stained for vimentin. Conversely, all 14 hypercellular microLMs were positive for vimentin, and only one (7%) was positive for alpha-smooth muscle actin and desmin. Five low-grade (38%) and 14 high-grade GISTs (35%) were positive for alpha-smooth muscle actin, and 12 low-grade (92%) and all 40 high-grade GISTs were stained for vimentin. CD34 was positive in 10 hypocellular microLMs (19%), all 14 hypercellular microLMs, 10 low-grade GISTs (77%), and 38 high-grade GISTs (95%). Hypercellular microLM thus showed similarities to clinical GIST and also exhibited significantly higher proliferation activity than hypocellular microLM on analysis of the Ki-67 labeling index and argyrophilic nucleolar organizer regions staining. The findings indicate that the hypercellular microLM may be a direct precursor for clinical GIST, both showing a primitive mesenchymal cell nature.

Cell Division↗
PubMed1997

Apoptosis, cell proliferation and expression of Bcl-2 and Bax in gastric carcinomas: immunohistochemical and clinicopathological study.

To clarify the relation between bcl-2 and bax protein (Bcl-2 and Bax) expression with regard to apoptosis and cell proliferation, 82 gastric carcinomas were immunohistochemically investigated. The significance of apoptosis for biological behaviour of the tumours was also examined. The apoptotic indices (AIs) were significantly lower in early-stage than in advanced-stage lesions (P<0.05), being positively correlated with the mitotic indices (MIs) (r=0.447, P<0.001). No association between either AIs or MIs and tumour size (diameter of intramural spreading) was noted. The AIs in the high Bcl-2-immunoreactive score group were significantly smaller than in either the low or the negative categories, whereas they were relatively elevated in the high Bax score group. In addition, an inverse correlation between Bcl-2 and Bax expression was revealed for both AIs and MIs. Although depth of tumour invasion and lymph node status were clearly associated with favourable outcome, no relation between survival rates and average values of either AIs or MIs, or immunoreactive scores for Bcl-2 and Bax was observed. These results indicate that in gastric carcinomas, apoptosis is closely associated with cell proliferation and expression of Bcl-2 and Bax, but appears likely to have no particular biological significance as a prognostic factor.

Adenocarcinoma↗
PubMed1997

Ki-67, p53, and Bcl-2 expression of serrated adenomas of the colon.

To investigate epithelial cell proliferation and oncoprotein expression of the serrated adenoma, a term that has been used synonymously with mixed hyperplastic and adenomatous polyp, immunohistochemical staining using polyclonal antibodies against Ki-67 and p53, and a Bcl-2 monoclonal antibody, was performed and the results compared with those in hyperplastic polyps and tubular adenomas. A total of 20 serrated adenomas all characterized by a serrated glandular pattern, contained immature goblet cells, upper crypt zone mitotic figures, and a few nucleoli within the epithelial cells. Twenty hyperplastic polyps and 20 tubular adenomas (all with low-grade dysplasia) were examined, and lesions that contained separate areas of hyperplastic and adenomatous glands were excluded. The Ki-67-positive rate in the middle zone of the crypts in serrated adenomas was significantly higher than in hyperplastic polyps but lower than in tubular adenomas; a similar tendency was also noted for the upper zone. Both serrated adenomas and hyperplastic polyps demonstrated Bcl-2-positive reactivity that was essentially limited to the lower crypt zone, while in contrast, involvement in tubular adenomas often extended to the middle zone. No p53 overexpression was found in any category. These results suggest that serrated adenomas may be committed to independent growth.

Adenoma↗
PubMed1997

Significant correlation of telomerase activity in thyroid papillary carcinomas with cell differentiation, proliferation and extrathyroidal extension.

Telomerase activity was examined by telomeric repeat amplification protocol assay in thyroid disease states, including adenomas and carcinomas, and correlated with clinicopathological features. Of a total of 26 papillary carcinomas, 16 cases (61.5%) were positive, with the poorly differentiated subtype being predominant (P < 0.05). A significantly more shortened terminal restriction fragment length (P < 0.05), higher incidence of extrathyroidal extension (P < 0.001), and more elevated Ki-67 labeling indices (P < 0.002) were also found in telomerase-positive than in telomerase-negative papillary carcinomas. Of four follicular carcinomas, 3 cases (75.0%) were positive. Positive telomerase activity in follicular adenomas (9/23 cases, 39.1%) and lymphocytic thyroiditis (12/22 cases, 54.5%) appeared to be mainly caused by infiltrating lymphocytes. However, three cases of atypical adenoma with relatively increased Ki-67 labeling indices were positive, suggesting a possibility of malignant potential. The good correlations with extrathyroidal invasiveness, Ki-67 labeling indices and poor differentiation of papillary carcinomas, established by multivariate analysis, suggest that this parameter might have potential application in the estimation of tumor progression and prognosis, and in clinical management.

Adenoma↗
PubMed1997

Detection of the Epstein-Barr virus genome in cervical neoplasia is closely related to the degree of infiltrating lymphoid cells: a polymerase chain reaction and in situ hybridization approach.

To cast light on the significance of Epstein-Barr virus (EBV) infection in cervical tumorigenesis, 44 cervical intraepithelial neoplasia (CIN) types I/II, and 70 CIN III lesions, 60 invasive squamous cell carcinomas (ISCC), and 20 normal cervical samples were investigated by polymerase chain reaction (PCR) and RNA in situ hybridization (RISH) assays. The EBV genome was detected by PCR using primers targeting the IR region in three (6.8%) of the CIN I/II, 15 (21.4%) of the CIN III and 13 (21.7%) of the ISCC lesions, while using an EBER oligonucleotide probe RISH revealed positive signals in infiltrating lymphocytes located in the cervical stroma, but not in dysplastic or tumor cells. There was a significant correlation between the presence of EBV DNA and the degree of lymphoid cell infiltration (P = 0.0223). In contrast, none of the normal cervical samples that were without inflammation demonstrated any EBV infection. Thus, the results indicated that a positive result for EBV on PCR may be simply dependent on the amount of lymphocytes in cervical stroma, suggesting that this virus does not play a major role in the etiology of cervical neoplasia.

Carcinoma, Squamous Cell↗
PubMed1997

Pulmonary alveolar proteinosis: diagnosis using routinely processed smears of bronchoalveolar lavage fluid.

AIMS: For the diagnosis of pulmonary alveolar proteinosis from bronchoalveolar lavage specimens it is normally necessary to make an ultrastructural examination. However, this is thought to be impractical for bronchoalveolar lavage specimens that have been routinely fixed in ethanol. In the present study, bronchoalveolar lavage cytology smears on slide glasses were examined directly ultrastructurally to make a diagnosis of pulmonary alveolar proteinosis. METHODS: Bronchoalveolar lavage smears from three pulmonary alveolar proteinosis patients were stained with Papanicolaou and periodic acid-Schiff (PAS) for identification of amorphous globular structures. Subsequently, they were refixed with glutaraldehyde and osmium tetroxide, and embedded in epoxy resin. Ultrathin sections were cut and examined ultrastructurally. RESULTS: Papanicolaou stained specimens from pulmonary alveolar proteinosis patients contained scattered amorphous or granular globules, 20-50 microns in diameter, which were PAS positive. Ultrastructural examination of the globules revealed multilamellated structures, characteristic of pulmonary alveolar proteinosis, in all cases. CONCLUSIONS: In general, it is thought that the morphological diagnosis of pulmonary alveolar proteinosis from bronchoalveolar lavage specimens requires both cytological and ultrastructural examination. However, the amorphous globules evident on cytology smears proved to contain multilamellated structures so that they can themselves be used as diagnostic evidence.

Adult↗
PubMed1997

Absence of human papillomavirus genomic sequences detected by the polymerase chain reaction in oesophageal and gastric carcinomas in Japan.

AIMS: To estimate the occurrence of human papillomavirus (HPV) infection in oesophageal or gastric carcinomas in patients in Japan. METHODS: 103 oesophageal and 99 gastric carcinomas were investigated by polymerase chain reaction (PCR) assays using two consensus (targeting either the L1 or the E6-E7 regions) and two type specific (type 16 and 18) primer sets. A beta globin gene specific primer set was also applied to examine the quality of the extracted DNA. RESULTS: Amplification of beta globin gene was clearly visible in 92 (89.3%) of the 103 oesophageal, and 89 (89.8%) of the 99 gastric carcinoma specimens. However, the entire series of tumour DNA was negative for HPV sequences by PCR assay using all four primer sets. CONCLUSION: HPV is not likely to be involved in oesophageal or gastric tumorigenesis in Japanese patients.

Adenocarcinoma↗
PubMed1997

Comparison of necrosis and fibrotic repair after ethanol injection between normal and cirrhotic livers.

To study the effects of percutaneous ethanol injection therapy on livers, we investigated necrotic changes after ethanol injection and fibrotic changes during the repair process in cirrhotic livers in comparison with normal livers. Male rats were treated with oral doses of 3'-methyl-4-dimethylaminoazobenzene and thioacetamide to produce liver cirrhosis. Both control animals and cirrhotic animals were injected with 0.2 ml of absolute ethanol into livers. Histological samples were cut serially, and the maximum areas of necrosis and fibrosis were measured until 28 days after the injection. Although the maximum area of necrosis was not different between cirrhotic livers and control livers, the average fibrotic ratio [(maximum fibrotic area/maximum necrotic area + maximum fibrotic area) x 100] was 64% in control livers (n = 9) and 40% in cirrhotic livers (n = 9; p < 0.05). The fibrotic repair process after ethanol injection seems to be impaired in cirrhotic livers as compared with normal livers.

Animals↗
PubMed1997

Enhanced cellular proliferation and p53 accumulation in gastric mucosa chronically infected with Helicobacter pylori.

This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) I:II ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Chronic persistent H pylori infection was associated with a low PG I:II ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma.

Adult↗
PubMed1997

Preventive effect of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil on colonic carcinogenesis induced by 1,2-dimethylhydrazine in rats.

Thymidylate synthetase (TS) and thymidine kinase (TK) are key enzymes in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. A high incidence of colorectal adenocarcinomas with varied grades of cell differentiation can be induced by 1,2-dimethylhydrazine (DMH) in rats. The marked increases of TS and TK activities were found in the poorly and well-differentiated adenocarcinomas of the colon, respectively. Oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) markedly reduced the number and accumulated area of colonic carcinomas, and TS activity in the poorly differentiated adenocarcinomas. A potential balance between the de novo and the salvage pathways for pyrimidine nucleotide synthesis was suggested to be related with the histopathological grades of cell differentiation. Suppression of colonic TS activity by UFT administration reduced the colonic carcinogenesis and the potency of the poorly differentiated adenocarcinomas of the colon.

1,2-Dimethylhydrazine↗