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Biomedical subjects

O Ishikawa

Publications and source records attributed to O Ishikawa.

At least 109 records · Page 6Linked to original sources
PubMed1997

Increased endothelial cell retraction and tumor cell invasion by soluble factors derived from pancreatic cancer cells.

BACKGROUND: Tumor cells induce endothelial cell retraction before invasion. In pancreatic cancer cells, the factors affecting endothelial cell retraction are not well-understood. METHODS: The activities of the endothelial cell retraction in conditioned media (CM) derived from three human pancreatic cancer cell lines, PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular junctional transport of FITC dextran through an endothelial cell monolayer in a transwell cell culture system. RESULTS: The CM derived from the three pancreatic cancer cells induced endothelial cell retraction. The endothelial cell retraction activity in the CM from PSN-1 cells was significantly higher than those from MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells enhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial cell retraction activity in the CM from PSN-1 cells were characterized as heat-stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in molecular weight, and were found both in heparin-bound and unbound fractions. CONCLUSIONS: PSN-1 cells produced and secreted at least two factors inducing the endothelial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.

Cell Adhesion↗
PubMed1997

Practical grouping of positive lymph nodes in pancreatic head cancer treated by an extended pancreatectomy.

BACKGROUND: Until recently long-term survival has not been expected when at least one positive node was detected at any site in pancreatic head cancer treated by conventional pancreatectomy. However, even when nodal involvement is seen, there has been an increasing number of long-term survivors after extended pancreatectomy in which a wide range of lymphatic and connective tissues were cleared. Thus the purpose of the present study was to establish a practical rational grouping of positive lymph nodes in pancreatic head cancer treated by extended pancreatectomy. METHODS: In 81 patients who tolerated extended pancreatectomy for cancer of the pancreatic head, a mean of 56 +/- 23 (range, 28 to 89) lymph nodes in each patient were examined under a microscope to determine the presence or absence of cancer. They were classified anatomically into 14 lymph node groups, and the incidence, distribution, and number of positive nodes were examined. A simplified grouping was made on the basis of the histologic findings and was checked against long-term survival rates. RESULTS: Nodal involvement was detected in 59 (73%) of 81 patients, and positive nodes were more commonly observed in the posterior pancreaticoduodenal (PPD), superior mesenteric (SM), and anterior pancreaticoduodenal (APD) groups than in the 11 other groups (p < 0.05). The PPD, APD, and SM groups offered the sole sites of nodal involvement with incidence levels of 23%, 17%, and 6%, respectively, whereas none of the 11 other groups did. Thus patients were classified into four groups: (a), negative in all 14 lymph node groups (n = 22); (b), positive but limited to the PPD/APD groups (n = 14); (c), also positive in the SM group, but negative in the 11 other groups (n = 13); and (d), also positive in at least one of the 11 other groups (n = 32). This classification was associated well with the 5-year survival rate: 59% in group (a), 53% in group (b), 15% in group (c), and 0% in group (d) [p < 0.05; group (b) versus group (c)]. Also this grouping associated well with the total number of positive nodes (p < 0.05). The 5-year survival rate in patients with one to three positive nodes was 47% and was more than 6% in patients with four to seven positive nodes (p < 0.05). CONCLUSIONS: In the clinicopathologic staging of the lymphatic spread from carcinoma of the pancreatic head, the PPD and APD groups were considered the first stations of lymphatic metastasis, whereas the 12 other groups-including the SM group-were categorized as second or more distant stations.

Humans↗
PubMed1997

Association of cumulative allelic losses with tumor aggressiveness in hepatocellular carcinoma.

BACKGROUND/AIMS: Loss of heterozygosity on various chromosomal arms has been reported in hepatocellular carcinoma and a multistep accumulation of genetic alteration has become accepted as the mechanism underlying progression of the disease. Although cumulative genetic alterations may imply more malignant tumors with poorer prognosis, the assumption requires further investigation. METHODS: Presence of loss of heterozygosity was analyzed by microsatellite markers at 13 loci on six chromosomal arms in 56 hepatocellular carcinomas. Association with cumulative allelic losses and prognosis of the patient following curative resection was studied. RESULTS: Frequency of allelic losses at each chromosomal arm was 31% on 1p, 20.6% on 4q, 17.5% on 8p, 17.5% on 13q, 25.5% on 16q and 17.4% on 17p. Thirty-three tumors (59%) presented loss of heterozygosity. Tumors with more allelic losses were significantly more likely to be un-infected by hepatitis C virus, and to be histologically poorly differentiated, to have higher alpha-feto protein value, to be advanced in T classification and in tumor stage. Patients with more than one loss of heterozygosity revealed poorer 3-year disease-free survival than those with one or no (p=0.0004). A multivariate Cox model analysis revealed cumulative loss of heterozygosity as an independent and influential factor for disease recurrence (relative risk, 2.66; 95% confidence interval, 1.23-5.75; p=0.013), followed by tumor stage. CONCLUSIONS: Cumulative loss of heterozygosity reflects the multistep genetic mechanism of progression of hepatocellular carcinoma. The study confirms the potential significance of genetic analysis in the management of the disease.

Adult↗
PubMed1997

Usefulness of simple endoscopic aspiration cytology of pancreatic juice for diagnosis of early pancreatic neoplasm. A prospective study.

For detection of early cancer of the pancreas, endoscopic aspiration cytology of pancreatic juice without endoscopic retrograde pancreatography was performed in 64 consecutive outpatients who had symptoms or findings that suggested pancreatic disease. Patients with positive or suspicious cytologic results or abnormal US findings were admitted and underwent detailed examinations. Positive and suspicious cytologic results were obtained in 2 and 10 patients, respectively. Of those with positive and suspicious cytologic results, two, and one patient, respectively, were ultimately found to have pancreatic neoplasms. Of these three resected specimens, one was in situ carcinoma and two presented marked atypia. All patients were alive with no evidence of recurrence. No further cases of pancreatic neoplasm were found. Complications from the procedure did not develop in any patient. This technique is useful in the diagnosis of early neoplasms of the pancreas, because it is simple and safe to perform for outpatients.

Aged↗
PubMed1997

The comparative study of anti-double stranded DNA antibody levels measured by radioimmunoassay and enzyme-linked immunosorbent assay in systemic lupus erythematosus.

Anti-double stranded (ds) DNA antibody is an autoantibody specific for systemic lupus erythematosus (SLE). For the measurement of this antibody, radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) is widely used in Japan. We studied the correlation of anti-dsDNA levels in 158 sera from 53 SLE patients between RIA and ELISA. The correlation coefficient between anti-dsDNA antibody levels measured by RIA and ELISA was 0.736 (p < 0.001). The concordance rate of sera with both ELISA/RIA-positive or both ELISA/RIA-negative results was 82.3% (130/158 sera). Twenty sera (12.7%) of 14 patients were ELISA-positive but RIA-positive, and 8 sera (5.0%) of 6 patients were ELISA-negative but RIA-positive. Our results suggest that both methods may be equally reliable for the detection of anti-dsDNA antibodies and that ELISA may be more sensitive than RIA. ELISA may be preferable because of its simplicity and convenience of the measurement procedure. The correlation coefficient between anti-ssDNA levels measured by ELISA and anti-dsDNA levels measured by RIA was 0.322 (p < 0.01), and the correlation coefficient between anti-ssDNA and anti-dsDNA antibody levels measured by ELISA was slightly higher, 0.515 (p < 0.001). These results may reflect the predominance of anti-DNA antibodies reactive with both ss and dsDNA in SLE sera. Since the clinical significance of anti-ssDNA antibodies remains unclear, further analysis of accumulated cases is required.

Antibodies, Antinuclear↗
PubMed1997

Plantar thrombotic nodules with marked neovascularization in diabetes: a symptom which has been overlooked?

A 69-year-old woman with diabetes has had multiple subcutaneous nodules on the soles for 11 months. She suffered from uncontrolled diabetes mellitus, hypercholesteremia, and cardiovascular thrombosis and had a past history of photocoagulation therapy for proliferative diabetic retinopathy. Histological examination revealed vascular thrombosis surrounded by neovascularization in the subcutaneous tissue. The basement membranes of vessels were thickened and strongly stained with periodic acid-Schiff. An increased serum concentration of von Willebrand factor antigen was observed. With control of her diabetes, the nodules almost disappeared. Her curious skin manifestation is speculated to be a diabetes-mellitus-related change in which endothelial injury and the subsequent induction of angiogenetic factors may play important roles. It is possible that this kind of skin manifestation has been overlooked or not examined histopathologically.

Aged↗
PubMed1997

Pneumomediastinum and subcutaneous emphysema associated with fatal interstitial pneumonia in dermatomyositis.

We described a 65-year-old woman who died of acute interstitial pneumonia associated with dermatomyositis. Subcutaneous emphysema and pneumomediastinum simultaneously developed. The association of the pulmonary rupture with vasculitis has been assumed as the common cause in interstitial pneumonia. Diffuse alveolar damage, however, might have led to the pneumomediastinum and subcutaneous emphysema in our patient, who had no signs of cutaneous vasculitis.

Aged↗
PubMed1997

Increased telomerase activities in human pancreatic duct adenocarcinomas.

Telomerase is a key enzyme with regard to immortalization of cancer cells and increased activity has been demonstrated in various human malignant neoplasms. Since little is known of its role in pancreatic cancers, we investigated changes in telomerase activity in human pancreatic duct adenocarcinomas and compared the frequency of increased telomerase activity with the presence of K-ras gene mutations. The samples were obtained from 38 pancreatic duct adenocarcinomas and 7 tumor surrounding tissues at surgical resection. Telomerase activity was examined by telomeric repeat amplification protocol assay and terminal restriction fragment (TRF) length was examined by Southern analysis. K-ras mutation was examined by means of polymerase chain reaction-single strand conformation polymorphism analysis. Among 38 pancreatic carcinomas, 32 (84%) exhibited increased telomerase activities with no apparent relation to the histological type of tumor, tumor size, regional lymphnode involvement and distant metastasis or clinical stage. In tissue surrounding the tumor, telomerase activity was not detected. TRF length tended to be reduced in pancreatic carcinomas. Mutations of K-ras gene were found in 24 out of the 38 (63%) cases. Among the 38 cases, 14 showed increased telomerase activity without K-ras mutation and 4 cases showed K-ras mutation without telomerase activity. These results suggest that increased telomerase activity might be a sensitive genetic diagnostic marker and could be a target for future therapy of pancreatic duct carcinomas.

Biomarkers, Tumor↗
PubMed1997

65-kilodalton protein phosphorylation in human peripheral blood eosinophils.

To evaluate the presence of protein phosphorylation in peripheral blood eosinophils, venous blood was drawn from normal healthy volunteers. Eosinophils were isolated on a Percoll gradient and were incubated with [gamma32P]ATP in the presence of Mg2+. After stopping the reaction, SDS-PAGE was performed and autoradiographs were prepared to determine the incorporation of 32P into proteins. Eosinophils developed at least 24 protein bands below 116.25 kD by SDS-PAGE. In the autoradiographs, one distinct radioactive band was observed with a molecular weight of 65 kD. 32P incorporation into the 65-kD band was dependent on Mg2+ concentration and maximal response was observed at concentrations of 2-6 mM MgCl2. 32P incorporation into the band was dependent on the reaction time and temperature of the reaction system. Acid hydrolysis showed that [32P]phosphate radioactivity in the cells was present primarily as phosphoserine, indicating the presence of 65-kD protein phosphorylation in human peripheral blood eosinophils.

Adult↗
PubMed1997

Disaccharide analysis of skin glycosaminoglycan in localized scleroderma.

BACKGROUND: Altered metabolism of skin glycosaminoglycan has rarely been investigated in localized scleroderma in contrast to systemic sclerosis. OBJECTIVE: The aim of this investigation is to elucidate the change in skin glycosaminoglycan of localized scleroderma. METHODS: We analyzed 5 skin samples of localized scleroderma and 10 site-matched control skin samples using high performance liquid chromatography after 1-phenyl-3-methyl-5-pyrasolone labeling. RESULTS: The involved skin constantly showed an increased amount of delta Di-4S(DS), the main disaccharide unit of dermatan sulfate, a decreased amount of delta Di-HA, the main disaccharide unit of hyaluronic acid, and an elevated ratio of delta Di-4S(DS)/delta Di-HA as compared with the uninvolved skin or the site matched control skin. CONCLUSION: These results correlate well with those findings in systemic sclerosis, indicating that the alteration in skin GAG may be closely related to the fibrotic process.

Adult↗
PubMed1997

Expression of carbohydrate antigen sialyl Le(a): a new functional prognostic factor in gastric cancer.

PURPOSE: The prognostic value of the altered expression of carbohydrate antigens sialyl Le(a) (sLe(a)) and sialyl Le(x) (sLe(x)), which have been implicated as functional ligands in heterotypic-cell-adhesion systems in the multistep process of tumor metastasis, were evaluated. PATIENTS AND METHODS: The level of expression of sLe(a) and sLe(x) antigens was examined immunohistochemically in paraffin-embedded tumor samples from 137 patients who underwent resection for gastric cancer. Correlation between the antigens' expression, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. RESULTS: Tumors that were positive for the sLe(a) antigen were significantly more likely to be large (P = .035), to be localized at the proximal third of the stomach (P = .018), to have an infiltrate appearance (P = .013), to have an invasive mode both in depth of invasion (P = .028) and in lymphatic invasion (P = .002), and to be classified as late stage (P = .011) than those that were negative for sLe(a), whereas the sLe(x) antigen status was not correlated with any clinicopathologic factors. The overall survival of patients with an sLe(a)-antigen-positive tumor was significantly poorer than that of those with an sLe(a)-antigen-negative tumor (P = .0001). Survival within each pathologic stage differed also (stage I, P = .030; stage II, P = .046; stage III, P = .026, respectively). A Cox regression analysis with multiple covariates showed that positive sLe(a) antigen status was an independent prognostic factor for a worse outcome in patients with gastric cancer. According to the mode of recurrence, increased sLe(a) antigen expression significantly affected both peritoneal dissemination and liver metastasis. CONCLUSION: Increased expression of the sLe(a) antigen may serve as a potent prognostic indicator for recurrence in patients with gastric cancer. Careful follow-up and intensive therapy are required for patients with an sLe(a)-antigen-positive gastric cancer.

Adenocarcinoma↗
PubMed1997

Flow cytometric DNA content analysis of ultraviolet light-induced squamous cell carcinomas: a comparative study of squamous cell carcinomas of the lip and those arising from other sites of sun-damaged skin.

The development of squamous cell carcinoma (SCC) of the lip is considered to be mainly related to excessive sun exposure. However, its higher metastatic rate is distinct from that of SCCs arising from other sites of sun-damaged skin. Flow cytometric DNA content analysis, using paraffin-embedded specimens, was performed on 15 SCCs of the lip and 32 SCCs arising from other sites of sun-damaged skin. A significantly lower incidence of DNA-aneuploidy was observed in SCCs of the lip (2/15) than in those of sun-damaged skin (15/32) (p < 0.05). The mean age of patients with SCC of the lip (66.7 +/- 11.6 years; mean +/- SD) was significantly lower than that of the other patients (78.1 +/- 11.1 years) (p < 0.01). There was no significant difference between the mean diameter size of tumors on the lip (19.5 +/- 5.7 mm) and that of tumors on other sites of sun-damaged skin (30.7 +/- 20.5 mm). These results suggest that additional carcinogenic factors besides ultraviolet light may be involved in the development of SCC of the lip.

Adult↗
PubMed1997

Morphological and biochemical analyses on fibroblasts and self-produced collagens in a novel three-dimensional culture.

The addition of L-ascorbic acid 2-phosphate (Asc 2-P), which is active and stable under a conventional culture condition, could render dermal fibroblasts to the organization of a dermis-like structure on a plastic dish without any prior treatment. The cell layer was composed of multilayered fibroblasts surrounded by dense extracellular matrices. Confocal microscopic examination disclosed that the fibroblasts in the upper layer were spindle-shaped and those in the lower layer were polygonal. Electron microscopic examination revealed the accumulation of mature collagen fibrils in the intercellular space. These morphological observations suggest that the cell layer may resemble the dermis-like structure. Biochemical analyses revealed that the hydroxyproline content of the cell layer increased in a time-dependent manner, while the monolayer culture system without. Asc 2-P yielded no measurable amount of hydroxyproline. On sodium dodecylsulphate-polyacrylamide gel electrophoresis, neutral insoluble collagens extracted from the cell layer showed the identical electrophoretic pattern to those from the human dermis. In addition, these bands were completely digested by bacterial collagenase. This novel culture system could provide a simple tool with which to investigate the collagen metabolism by fibroblasts under more physiological conditions.

Adolescent↗
PubMed1997

The presence of anti-basement membrane zone antibodies in the sera of patients with non-bullous lupus erythematosus.

We performed indirect immunofluorescence (IF) studies using 1 mol/l sodium chloride split skin to determine whether or not a positive IF is specific to patients with bullous lupus erythematosus (LE). We examined the sera from 21 patients with systemic LE (SLE), three of which were obtained from two SLE patients and one subacute cutaneous LE (SCLE) patient with bullous eruptions. As a comparison, we also studied the sera from patients with discoid LE (DLE, n = 7), SCLE (n = 1), systemic sclerosis (SSc, n = 20), bullous pemphigoid (n = 2) and normal individuals (n = 10). Sera from 16 SLE, four DLE and two SSc revealed a linear deposition of IgG isotype antibody at the epidermal side and/or the dermal side on indirect IF of split skin. The sera from three patients with bullous eruption and from 12 patients of SLE, SCLE, DLE without bullous eruption or SSc were further analysed by immunoblotting using five defined antigens, i.e. dermal extract, epidermal extract, three fusion proteins of 230 kDa bullous pemphigoid antigen (BPAG). 180 kDa BPAG, and human epidermolysis bullosa acquisita (EBA) antigen. Two SLE sera as well as one of the SCLE and the DLE serum reacted with 230 kDa BPAG in epidermal extract, and one of the SCLE and the DLE serum also reacted with the fusion protein of 180 kDa BPAG. No serum reacted with the dermal extract or the fusion protein of 230 kDa BPAG or EBA antigen. There was no consistent correlation between split-skin IF results and immunoblotting results. These results may suggest that even non-bullous LE patients often have autoantibodies to the basement membrane zone antigens, most of which are less pathogenic. Although we rarely examine the sera from non-bullous LE patients, we should keep this phenomenon in mind to avoid overestimating the results of split-skin test and immunoblotting.

Adult↗
PubMed1997

[PyNPase activity in primary and metastatic colorectal cancer].

5'-Deoxy-5-fluorouridine (5'-DFUR) is converted to 5-FU by the enzyme of Pyrimidine nucleoside phosphorylase (PyNPase). Its efficacy for lung metastases from colorectal cancer is known. So we investigated PyNPase activity in primary and metastatic lesions of colorectal cancer patients. The results revealed that PyNPase activity (microgram 5-FU/mg protein/hour) (mean +/- SD) was 122.1 +/- 61.1 (n = 48) in primary lesions, 91.6 +/- 48.3 (n = 4) in lymph node metastases, 135.2 +/- 56.4 (n = 10) in liver metastases and 168.2 +/- 79.8 (n = 11) in lung metastases. In non-cancerous tissues adjacent to the cancer lesions, PyNPase activity was 51.5 +/- 18.8 in normal colorectal mucosa, 61.8 +/- 24.7 in normal liver and 43.0 +/- 21.2 in normal lung. These results demonstrated that PyNPase activity in the cancer lesions reached significantly higher levels than in the non-cancerous tissues (p < 0.01); and the T/N ratio of PyNPase activity in lung was also significantly higher than in primary or other metastatic lesions (p < 0.05). It was surmised that the clinical response of colorectal cancer to 5'-DFUR had been influenced by PyNPase activity.

Adenocarcinoma↗