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Biomedical subjects

O Ishikawa

Publications and source records attributed to O Ishikawa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Cyclic AMP specific phosphodiesterase activity and colon cancer cell motility.

To investigate mechanisms for regulation of intracellular cAMP involved in cancer cell invasion, phosphodiesterase (PDE) activity in a colon cancer cell line, DLD-1, was studied. Activities of PDE 2, 4, and 5 were detected in DLD-1 cells by pharmacological approach. Specific and cell permeable inhibitors for those PDEs were used to determine which PDE is responsible for cAMP turnover involved in cancer cell motility. Treatment of DLD-1 cells with rolipram and Ro-20-1724 inhibitors for PDE 4, elevated intracellular cAMP contents three to five times of control. EHNA, an inhibitor for PDE 2, and zaprinast. an inhibitor for PDE 5, did not affect cAMP levels. To assess cellular motility, we utilized chemotaxis assay. EHNA and zaprinast did not suppress serum-induced chemotaxis. In contrast, rolipram and Ro-20-1724, suppressed chemotaxis in a dose dependent fashion. These suggest that PDE 4 plays a critical role in regulating intracellular cAMP levels of colon cancer cells and is involved in cancer invasion. PDE 4 can be a novel target of anti-invasion drug.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Disaccharide analysis of skin glycosaminoglycans in atrophoderma of Pasini and Pierini.

There are divergent opinions as to whether atrophoderma of Pasini and Pierini (APP) is a nosologic entity or a primary atrophic morphoea. In this study, we used high performance liquid chromatography to analyse the skin disaccharide contents of glycosaminoglycan (GAG) in two patients with APP and compared the results with those from a typical atrophic morphoea patient. Perilesional uninvolved skin was used as a control in each patient. In the atrophic phase morphoea, both the total amount of disaccharide per skin punch-biopsy and the amount of DeltaDi-4S(DS) - the main disaccharide unit of dermatan sulphate - per mg dry weight were increased. These changes were consistent with sclerotic phase morphoea. In contrast, the total amount of disaccharide per skin punch-biopsy was decreased and the amount of DeltaDi-4S(DS) per mg dry weight was decreased or unchanged in APP. Our results suggest that GAG metabolism in APP may be unique and quite different from that in morphoea.

Adolescent↗
PubMed2000

Tufted angioma (angioblastoma): case report and review of 41 cases in the Japanese literature.

We report a 53-year-old man with a 2-year history of a violaceous indurated plaque on the shoulder. Although angiosarcoma was clinically suspected, histological examination revealed numerous lobules ('tufts') with cleft-like vascular lumina throughout the dermis and subcutaneous tissue. Tumour cells had no nuclear atypia and were positive for CD34, but almost negative for factor VIII-related antigen. These findings were compatible with a diagnosis of tufted angioma, or angioblastoma. We reviewed 41 cases reported in Japan and found that, although most patients presented during the first year of life (23/41), the condition does occur throughout childhood and adult life. Both sexes are affected equally and, contrary to some reports, it is unlikely that oestrogens have a pathogenic role.

Aged↗
PubMed2000

Synchronous esophageal and renal cell carcinoma.

Multiple cancer associated with esophageal cancer is not uncommon; however, synchronous esophageal and renal cell carcinoma is very rare. Only three cases have been reported to date, and one of these patients was treated in our institution. We have since successfully treated another patient. Here, we report the two cases treated in our institution. In the first case, esophagectomy, nephrectomy, and reconstruction using a gastric tube were carried out in one stage. Post-operative renal function was temporarily impaired by the complications of anastomotic leakage and pyothorax but no hemodialysis was needed. In the second case, as the patient had undergone distal gastrectomy because of gastric cancer, we chose a two-stage operation, i.e. esophagectomy and nephrectomy as the first stage, followed by reconstruction using a colon substitute after 4 weeks, resulting in only slight renal dysfunction. Patients 1 and 2 are alive and well 7 years and 2 years after the operations respectively.

Aged↗
PubMed2000

Hyaluronan exists in the normal stratum corneum.

Hyaluronan is well known to exist as a water-sorbed macromolecule in the extracellular matrix. We here examined whether hyaluronan exists in the normal stratum corneum. High performance liquid chromatography was used to quantify hyaluronan content in the stratum corneum, epidermis (including stratum corneum), and dermis of mice, with the resulting dry weights being 22.3 +/- 2.9, 15.1 +/- 1.5, and 738.6 +/- 31.6 microg per g, respectively. Normal mouse skin was then labeled with [3H]-glucosamine in an organ culture, and accumulation of [3H]-labeled hyaluronan and its molecular mass were determined separately for the stratum corneum, epidermis, and dermis. In the stratum corneum, [3H]-labeled hyaluronan was accumulated linearly over the 3-d culture period. After the 3-d culture period, the epidermis synthesized twice the amount (expressed as dpm per mg dry weight) of [3H]-labeled hyaluronan as the dermis, whereas the stratum corneum and dermis showed nearly the same content of [3H]-labeled hyaluronan. The molecular mass of [3H]-labeled hyaluronan was highest (>1.0 x 106) in the dermis and clearly lower (<6.0 x 104) in the stratum corneum. Based on these results, we here confirm that hyaluronan is supplied from keratinocytes beneath the stratum corneum layer, and is present in the normal stratum corneum. We speculate that hyaluronan may play a role in moisturizing the stratum corneum and/or regulating its mechanical properties.

Animals↗
PubMed2000

Effect of mast cell-derived mediators and mast cell-related neutral proteases on human dermal fibroblast proliferation and type I collagen production.

BACKGROUND: Possible involvement of mast cells in various fibrotic conditions has been suggested, but the relative contribution of each mast cell mediator and neutral protease to fibroproliferative activity remains to be elucidated. OBJECTIVE: We investigated the effect of mast cell-derived mediators and mast cell-related neutral proteases on type I collagen production and proliferation by human dermal fibroblasts. METHODS: Mast cell-derived mediators or neutral proteases were added to cultured fibroblasts from normal dermis, and cell proliferation and type I collagen synthesis were assayed. RESULTS: Fibroblast proliferation was increased by 2.8 x 10(-9) mol/L prostaglandin D(2) and 10 microgram/mL carboxypeptidase A, but not by leukotriene D(4) or cathepsin G at the concentrations studied. Proliferation was increased by tryptase in a concentration-dependent manner, and a significant increase was observed at concentrations of 1 and 10 microgram/mL. Production of type I collagen by fibroblasts was increased in the presence of 2.0 x 10(-9) mol/L leukotriene D(4) and 10 microgram/mL tryptase. CONCLUSION: Mast cell-derived mediators prostaglandin D(2) and leukotriene D(4) and mast cell-related neutral proteases carboxypeptidase A and tryptase increase the proliferation and type I collagen production of human dermal fibroblasts in various manners.

Cell Division↗
PubMed2000

Influence of IgE-mediated activation of cultured human mast cells on proliferation and type I collagen production by human dermal fibroblasts.

BACKGROUND: Mast cells have been suggested to be involved in fibrotic conditions, but it still remains unknown whether IgE-mediated activation of human mast cells promotes fibrogenesis by human fibroblasts. OBJECTIVE: The purpose of this study was to determine whether IgE-mediated activation of cultured human mast cells can promote fibrogenesis by cultured human dermal fibroblasts. METHODS: Mast cells derived from human umbilical cord blood cells were incubated with IgE and then activated by anti-IgE, and histamine release was measured. IgE-sensitized mast cells were cocultured with fibroblasts from normal dermis and activated with anti-IgE to induce histamine release, after which proliferation and type I collagen synthesis by the fibroblasts were determined. RESULTS: Coculture of subconfluent human dermal fibroblasts with IgE-sensitized mast cells did not affect fibroblast proliferation. However, fibroblast proliferation was increased by activated mast cells, and a significant increase was observed in the presence of 10(5) or 3 x 10(5) mast cells/mL. The promotion of fibroblast proliferation by mast cells (3 x 10(5)/mL) was partly inhibited by ketotifen at a concentration that significantly reduced histamine release from mast cells. On the other hand, IgE-mediated activation of mast cells did not increase type I collagen production by confluent human dermal fibroblasts. CONCLUSION: IgE-mediated activation of cultured human mast cells could increase the proliferation of human dermal fibroblasts, but did not promote type I collagen production by the fibroblasts under the conditions tested.

Cell Division↗
PubMed2000

Reciprocal functions of liver tumor cells and endothelial cells. Involvement of endothelial cell migration and tumor cell proliferation at a primary site in distant metastasis.

BACKGROUND: The mechanism by which tumor cells interact with endothelial cells at the primary site in metastasis remains obscure. MATERIALS AND METHODS: To disclose the precise mechanisms and processes of metastasis and angiogenesis, we investigated the interactions of endothelial cells (CPAE; calf pulmonary arterial endothelial cells) with two mouse liver tumor cell lines, G-5, a highly metastatic clone, and G-1, a poorly metastatic clone, based on the difference in their angiogenic activities in vivo at a primary site. RESULTS: G-5 cell cultured conditioned medium (CM) promoted migration of endothelial cells more than did G-1 cell CM, in migration assay using modified Boyden chambers. Anti-basic FGF antibody inhibited G-5-induced endothelial cell migration. Furthermore, endothelial cells stimulated proliferation of G-5 cells more than that of G-1 cells in coculture assay using Transwell chambers (pore size; 0.4 microm). Pretreated endothelial cells with bFGF enhanced tumor cell proliferation, suggesting the ability of activated endothelial cells to support tumor growth. In addition, incubation with endothelial cell CM also improved the proliferative activity of G-5 cells more than that of G-1 cells in a concentration-dependent fashion, indicating production and secretion of liver tumor cell growth substance by endothelial cells. CONCLUSION: These results provide evidence that liver tumor cells stimulate endothelial cell migration and migrated endothelial cells facilitate liver tumor cell proliferation. Tumor growth at a primary site may initially be dependent on migrated endothelial cells rather than vascularization or blood nutrient supply. This bi-directional paracrine relationship between liver tumor cells and endothelial cells may influence their metastatic ability.

Animals↗
PubMed2000

Expression of N-acetylglucosaminyltransferase V in colorectal cancer correlates with metastasis and poor prognosis.

N-Acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes beta 1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cell proteins. Metastatic potential of various cancer cells has been shown to correlate with increase of GnT-V activity and concomitant beta 1-6 branching of N-acetylglucosamine. However, protein expression of GnT-V in human cancer tissue and its clinical significance have not yet been demonstrated. To clarify the possible relationship between metastasis and GnT-V in human colorectal cancer, protein expression of GnT-V was studied using surgically resected specimens. We established a monoclonal antibody against GnT-V and performed immunohistochemical analysis of 103 human colorectal cancer cases. Of 103 cases, 26 cases (25.2 %) showed specific expression of GnT-V in colorectal cancer tissues. The expression of GnT-V was significantly correlated with distant metastasis (P < 0.05, chi2 test). Overall 5-year survival rate was 52.8% for GnT-V-positive patients and 81.7% for GnT-V-negative patients (P < 0.01, Log-rank test). We showed direct evidence for the relationship between GnT-V and metastasis in human colorectal cancer. Screening of GnT-V expression in colorectal cancer may provide useful information for prognosis of postoperative patients.

Aged↗
PubMed1999

Phase II study of limited surgery for early gastric cancer: segmental gastric resection.

BACKGROUND: Endoscopic resection for treatment of early gastric cancer (EGC) is widely performed. Recently, however, surgeons began performing a limited operation for EGC when endoscopic resection was not indicated. This report discusses the surgical technique and the results of the limited operation, which is generally referred to as "segmental resection" (SR). METHODS: Since 1990, a total of 50 patients with intramucosal invasive EGC of the middle stomach underwent SR. The procedure included a limited gastrectomy, limited lymph node dissection, and preservation of the vagal nerve. We examined the surgical risk, postoperative complications, and patient survival rates and compared the results for the SR-treated patients (group A) with results for patients with EGC who underwent subtotal gastrectomy and systemic lymph node dissection (group B). RESULTS: Blood loss was less in group A (239 +/- 180 ml) than in group B (342 +/- 176 ml) (P < .05). The incidence of postoperative complications was also lower in group A (2.0%) than in group B (14.0%) (P < .05). The incidence of postoperative cholelithiasis was lower in group A (4.0%) than in group B (18.0%) (P < .05). All patients in both groups are alive without recurrence. CONCLUSIONS: Compared with distal gastrectomy, SR for EGC of the middle stomach decreased the surgical risk and postoperative complications without increasing the recurrence rate.

Female↗
PubMed1999

Evaluation of preoperative and intraoperative arterial stimulation and venous sampling for diagnosis and surgical resection of insulinoma.

BACKGROUND: The precise intraoperative localization of insulinoma is essential for successful surgical treatment. In addition to various imaging modalities developed recently, arterial stimulation and venous sampling (ASVS) has also been used for tumor localization. METHODS: Preoperative and intraoperative ASVS procedures were performed in 6 patients with insulinoma. Intraoperative ASVS was performed before and after tumor resection. Immunoreactive insulin (IRI) concentrations and the IRI ratio (IRI concentration at each time interval after calcium injection/baseline IRI concentration) were determined by the conventional or a quick IRI method. RESULTS: The site of the tumor was identified preoperatively in all patients. The peak of the IRI ratio varied widely, but setting the cutoff value at 3.0 clearly differentiated peak IRA ratios in feeding arteries from those of nonfeeding arteries. Intraoperative ASVS showed a similar elevation of IRI levels, but the elevation disappeared after tumor resection in all but 1 patient. In 2 patients, resection of the tumor was confirmed during surgery by measuring IRI levels by the quick IRI method. CONCLUSIONS: A combination of ASVS and conventional imaging modalities is useful for precise localization of insulinoma. Resection of the tumor can be confirmed intraoperatively by comparing IRI levels associated with preoperative and postresective ASVS.

Adult↗
PubMed1999

Influences of keratinocyte-fibroblast interaction on the expression of epimorphin by fibroblasts in vitro.

Epimorphin was demonstrated to be a mesenchymal signal factor modulating epithelial morphogenesis of skin, lung and liver in vitro. Most of the previous studies were performed biochemically and functionally. In the present study, expression of epimorphin was immunohistochemically compared between cultured fibroblasts and cocultured fibroblasts with keratinocytes obtained from normal skin. Cultured fibroblasts revealed a low level of epimorphin expression. In contrast, the expression by fibroblasts was greatly enhanced in skin explant culture where both fibroblasts and keratinocytes were present. In three-dimensional coculture of fibroblasts and keratinocytes, the expression of epimorphin was enhanced. The staining pattern of epimorphin in three-dimensional coculture was similar to that in human skin. These results suggest that dermal fibroblasts are manufacturers of epimorphin, and keratinocyte-fibroblast interaction may play important roles in the expression of epimorphin in vitro.

Adult↗
PubMed1999

Phosphodiesterase type III inhibitor, cilostazol, inhibits colon cancer cell motility.

Metastasis of cancer cells is initiated by the cellular migration into extracellular matrix and surrounding vessels. We previously showed that elevation of cAMP levels in cancer cells suppressed trans-cellular migration in vitro. Drugs that can elevate cAMP levels in cancer cells effectively may be applied to prevent metastasis in cancer patients. Cilostazol, an oral anti-platelet drug, is a specific cAMP phosphodiesterase type III inhibitor and has been clinically used to treat thrombosis patients. In chemotaxis assay, cellular migration of human colon cancer cells, DLD- 1, was induced by 10 microg/ml of soluble fibronectin or 10% of fetal bovine serum (FBS). Treatment with cilostazol (50 microM) suppressed 92.3% or 84.6% of the migration in control cells, respectively. When DLD-1 cells were stimulated by soluble fibronectin in phagokinetic assay, migration assessed by the area of gold particle phagocytosis track was induced and cilostazol also decreased 67.3% of the cellular migration in control cells. Furthermore, in the trans-cellular migration assay, cilostazol suppressed cancer cell invasion induced by FBS. Thus, cilostazol can suppress colon cancer cell motility and might be effective as an anti-metastasis drug for cancer patients.

Animals↗
PubMed1999

Cutaneous papules and nodules in the diagnosis of the antiphospholipid syndrome.

Of 11 patients with primary or secondary antiphospholipid syndrome (APS), four exhibited papules or nodules on the finger, sole or leg as the initial cutaneous manifestation. Histological examination demonstrated thrombosed vessels or vessels containing organized thrombi in the dermis or in the subcutaneous fat tissue. Cutaneous papules and nodules should be recognized as skin manifestations of APS. Screening tests for antiphospholipid antibodies and lupus anticoagulant are required in patients with cutaneous papules or nodules of unknown aetiology. In cases of positive antiphospholipid antibodies and/or lupus anticoagulant, histological examination is critical in the establishment of the diagnosis of APS.

Adolescent↗