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Osamu Ishikawa

Publications and source records attributed to Osamu Ishikawa.

At least 19 recordsLinked to original sources

Disaccharide analysis of glycosaminoglycans synthesized by cardiac myxoma cells in tumor tissues and in cell culture.

We analyzed the main disaccharide units of glycosaminoglycans synthesized by cardiac myxoma cells in vivo and in cell culture using high-performance liquid chromatography after 1-phenyl-3-methyl-5-pyrasolone labeling. Cardiac myxoma tissues contained large amounts of chondroitin-6-sulfate (46%) and hyaluronic acid (32%), along with some chondroitin-4-sulfate (13%), chondroitin (6%), and much less dermatan sulfate (3%). Cultured cardiac myxoma cells synthesized mainly chondroitin-6-sulfate. The abundant glycosaminoglycans in myxoma tissues may make up the characteristic friable gelatinous matrix which is favorable for embolism and tumor cell growth.

Adult↗

Role of the CD47-SHPS-1 system in regulation of cell migration.

SHPS-1 is a transmembrane protein whose extracellular region interacts with CD47 and whose cytoplasmic region undergoes tyrosine phosphorylation and there by binds the protein tyrosine phosphatase SHP-2. Formation of this complex is implicated in regulation of cell migration by an unknown mechanism. A CD47-Fc fusion protein or antibodies to SHPS-1 inhibited migration of human melanoma cells or of CHO cells overexpressing SHPS-1. Overexpression of wild-type SHPS-1 promoted CHO cell migration, whereas expression of the SHPS-1-4F mutant, which lacks the phosphorylation sites required for SHP-2 binding, had no effect. Antibodies to SHPS-1 failed to inhibit migration of CHO cells expressing SHPS-1-4F. SHPS-1 ligands induced the dephosphorylation of SHPS-1 and dissociation of SHP-2. Antibodies to SHPS-1 also enhanced Rho activity and induced both formation of stress fibers and adoption of a less polarized morphology in melanoma cells. Our results suggest that engagement of SHPS-1 by CD47 prevents the positive regulation of cell migration by this protein. The CD47- SHPS-1 system and SHP-2 might thus contribute to the inhibition of cell migration by cell-cell contact.

Animals↗

Prognostic significance of the size of cancer nests in metastatic lymph nodes in human esophageal cancers.

BACKGROUND: Postoperative survival of patients with esophageal cancers after curative surgery is strongly affected by the presence of lymph node metastasis. The number and location of lymph node metastases have been evaluated and graded, but the clinical significance of their size has not been well investigated. METHODS: Of 322 esophageal cancer patients who underwent curative operations with radical lymph node dissection, 170 (53%) had lymph node metastasis. A total of 784 metastatic lymph nodes were obtained, and the area of the cancer nests was measured microscopically in the cross section. The data from each patient included the area of the largest cancer nest in the positive nodes (Nmax), classified as Na (<4 mm2), Nb (4-25 mm2), Nc (25-100 mm2), or Nd (>100 mm2). RESULTS: The 170 patients were classified according to the Nmax value: Na, 31 (18.2%); Nb, 35 (20.5%); Nc, 49 (28.8%); and Nd, 55 (32.4%). The 5-year survival rate was 77.7% in patients without lymph node metastasis and 35.4% in those with lymph node metastasis. When classified by Nmax, the 5-year survival rate was 77.8% for Na, 63.9% for Nb, 18.8% for Nc, and 12.8% for Nd. There was no significant difference in the survival rate between Na patients and those without lymph node metastasis. Nmax showed significant correlation with the primary tumor size, depth of tumor invasion, and number and location of metastatic lymph nodes, but not with histologic type or primary tumor location. In multivariate analysis, the Nmax value, the number of lymph node metastases and depth of tumor invasion were independent prognostic factors, while the location of the lymph node metastases was not statistically significant. CONCLUSIONS: The area of the largest cancer nest in the lymph nodes was one of the most significant prognostic factors for esophageal cancers. This estimation is objective and reproducible and may be of great importance when deciding the therapeutic modality for patients with esophageal cancers.

Esophageal Neoplasms↗

Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas.

BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma (HCC) is poor because of frequent intrahepatic metastasis (IM) or multicentric carcinogenesis (MC). We compared the effectiveness of loss of heterozygosity (LOH) analysis in the diagnosis of these two forms with that of histopathological diagnosis. METHODS: Using LOH analysis of 15 specific DNA microsatellite loci, tumor clonality was assessed in 37 cases. RESULTS: LOH was observed in 30% of seven solitary tumors. According to these results, the selected threshold to diagnose MC was a difference in the LOH status at more than 30% of the analyzed loci, when comparing two samples in the same liver. In nine multiple HCCs, identical genetic and histopathological diagnoses were found in four (IM: 2, MC: 2). Of 21 recurrent tumors, 19 showed LOH for at least one marker. IM and MC were genetically diagnosed in five and ten patients, respectively. Genetic and histopathological diagnoses were identical in ten of 19 patients (IM: 5. MC: 5). Five genetic MC were histopathologically diagnosed as IM (3) and 'undetermined' (2). CONCLUSIONS: Genetic diagnosis by LOH analysis may be more strict and specific than histopathological diagnosis in the differential diagnosis of IM and MC.

Adult↗

Hypoxia-induced increase of matrix metalloproteinase-1 synthesis is not restored by reoxygenation in a three-dimensional culture of human dermal fibroblasts.

BACKGROUND: Delayed wound healing is multi-factorial. Although ischemic change is considered to be crucial, little is known about the effects of hypoxia or reoxygenation on the connective tissue metabolism by human dermal fibroblasts. OBJECTIVE: The aim of this study is to determine whether or not hypoxia (2% O(2)) or reoxygenation (20% O(2)) affects mRNA expression and production of matrix metalloproteinase-1 (MMP-1), type I collagen, tissue inhibitors of metalloproteinase-1 (TIMP-1), and transforming growth factor-beta1 (TGF-beta1) by human dermal fibroblasts in a three-dimensional culture. METHODS: We introduced the three-dimensional culture of human dermal fibroblasts with experimental wound. After wounding, cells were incubated under hypoxic (2%) or normoxic (20%) condition, and harvested at 24, 36, 48, and 72 h (n=8). In the reoxygenation study (n=4), cells were first exposed to a hypoxic condition for 72 h and further incubated under a normoxic condition for 72 h. RESULTS: The relative ratio (hypoxia/normoxia) of MMP-1 mRNA expressions were significantly elevated at 36 and 48 h compared with those at 12 h (P<0.05). The relative ratio of proMMP-1 was also significantly increased at 48 and 72 h compared with that at 12 h (P<0.001 and P<0.05, respectively). There were no significant changes in mRNA and protein levels of type I collagen, TGF-beta1, and TIMP-1. In a reoxygenic condition, 72 h reoxygenation after 72 h hypoxia, the hypoxia-induced alterations of MMP-1 and carboxyterminal propeptide of type I procollagen (PIP) were not restored. CONCLUSION: Our results indicate that hypoxia may be responsible for delayed wound healing by inducing an increase of MMP-1 synthesis.

Cells, Cultured↗

Six novel P gene mutations and oculocutaneous albinism type 2 frequency in Japanese albino patients.

Type 2 oculocutaneous albinism (OCA2) is an autosomal recessive disorder that results from mutations in the P gene that codes one of the melanosomal proteins, the function of which remains unknown. In this paper, we report the frequency of OCA2, 8%, among the Japanese albino population, six novel mutations containing four missense substitutions (P198L, P211L, R10W, M398I), and two splice site mutations (IVS15+1 G>A, IVS24-1 G>C). One of them, R10W, was within the putative signal peptide at the N-terminal of the P protein. This is the first report on the frequency of OCA2 in the Japanese albino population.

Adult↗

Possible indication for surgical treatment of squamous cell carcinomas of the esophagus that involve the stomach.

BACKGROUND: The caudal spread of esophageal squamous cell carcinoma (ESCC) frequently involves the stomach. An extended surgical treatment may provide a tumor-free margin; however, its clinical benefit has not been elucidated. METHODS: Sixty-three of 582 patients with ESCC (11%) had massive gastric involvement and underwent esophagectomy with combined resection of the stomach and other organs. The mode of gastric involvement was classified as direct invasion from primary tumor (PT invasion) or invasion from metastatic lymph nodes (LN invasion). RESULTS: In addition to the removal of either the proximal (83%) or the whole (17%) stomach, 46 patients (73%) underwent the combined resection of adjacent organs, including the diaphragm, pancreas, liver, lung, and pericardium. This surgical treatment resulted in a high rate (83%) of curative resection and a low rate (8%) of operative mortality. Postoperative survival rates were 53%, 33%, and 25% at 1, 2, and 5 years, respectively. The first tumor recurrence was frequently in the abdominal paraaortic lymph nodes (41%) and the liver (28%), followed by the mediastinal lymph nodes, local recurrence, the lung, and other organs. The mode of gastric involvement strongly affected clinical outcome, with a 5-year survival rate of 36% for those with PT invasion but of only 7% with LN invasion (P <.0086). No significant difference was seen in the number and location of metastatic lymph nodes between the 2 groups; however, the size of the largest metastatic lymph node was significantly smaller with PT invasion than with LN invasion (12 mm vs 37 mm in diameter; P <.0001). CONCLUSION: Surgical treatment of ESCC involving the stomach was considered safe and successful. A favorable prognosis can be expected for gastric invasion from the primary tumor but not from metastatic lymph nodes.

Carcinoma, Squamous Cell↗

Postoperative cytology for drained fluid from the pancreatic bed after "curative" resection of pancreatic cancers: does it predict both the patient's prognosis and the site of cancer recurrence?

OBJECTIVE: To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer. SUMMARY BACKGROUND DATA: The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy. METHODS: This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patient's survival, and mode of cancer recurrence, including local recurrence. RESULTS: Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence. CONCLUSIONS: Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.

Adenocarcinoma↗

[Epidemiological study on patients with systemic sclerosis receiving financial aid for treatment].

We conducted an epidemiological study of systemic sclerosis in Japan using the records of patients who had been registered to receive public financial aid. A total of 10,956 patients were registered as having systemic sclerosis in 1999. We statistically analyzed the data on the patients, including sex, age, major symptoms, and laboratory findings. We also made contingency tables in order to evaluate the correlations of the data. Our study estimated that the male/female ratio was 1:7.3. The mean ages of male and female patients were 58.8 and 58.5 years old, respectively. The major symptoms were as follows: Raynaud's phenomenon 92.4%, skin sclerosis 94.7%, dyspnea 29.9%, and dysphagia 32.2%. With respect to specific antibodies, antinuclear antibody was present in 92.2%, antitopoisomerase I antibody in 27.5%, anticentromere antibody in 37.7%, and antiribonucleoprotein antibody in 19.9%. Making contingency tables, we could elucidate the association of antitopoisomerase I with lung fibrosis.

Adolescent↗

[Phase III additional clinical study of 111In-pentetreotide (MP-1727): diagnosis of gastrointestinal hormone producing tumors based on the presence of somatostatin receptors].

Additional phase III multicenter clinical study was performed to investigate the efficacy, safety, and usefulness of somatostatin receptor scintigraphy using 111In-pentetreotide (MP-1727), which binds to somatostatin receptors. Forty patients were included in the study; Group A: 18 patients, gastrointestinal hormone producing tumors had been detected with conventional imaging modalities, Group B: 22 patients, no tumors had been detected with conventional imaging modalities in spite of high serum hormone levels. By comparing the results of the octreotide suppression test, 12/16 cases (75.0%) of Group A and 11/19 cases (57.9%) of Group B were assessed as "effective." By comparing the results of immunohistological examination, 5/9 cases (55.6%) of Group A and 2/4 cases (50.0%) of Group B were assessed as "effective." Severe adverse events were not observed in any of the evaluable 35 cases. MP-1727 was judged as clinically useful in 11/16 cases (68.8%) of Group A and 5/19 cases (26.3%) of group B. These results suggest that MP-1727 scintigraphy is very useful for the diagnosis and decision of the therapeutic strategy of gastrointestinal hormone producing tumors.

Aged↗

Enhancement of transdermal absorption by switching iontophoresis.

The enhancing effect of switching iontophoresis on transdermal absorption of phthalic acid (PA), benzoic acid (BA), salicylic acid (SA), p-phenylenediamine (PD), aniline (AN) and verapamil (VR) and its mechanism were examined. An electric current with pulsed waveform (4 kHz, 50% duty) was passed through the skin for 2 h at 10 V. Iontophoretic application was carried out with switching at intervals of 5, 10 and 20 min, or without switching. Each drug solution was injected into the donor side of the cell, and phosphate buffer (pH 7.4) was injected into the receiver side. Transport of PA, BA and VR was affected by switching the polarity of electrodes but no effect was observed on that of SA, PD and AN. Cumulative amount permeated and apparent permeability coefficients were apparently high at switching intervals with a short period. The partition coefficient suggested that there was no interrelation between the affinity for skin and the permeability of each drug. The resistance values of PA and glucose were low at intervals of 5 min suggesting the participation of enhanced hydration of the skin. These results suggested that enhancement of skin hydration plays an important role in the enhancing effect of switching iontophoresis on skin permeation.

Administration, Cutaneous↗

Expression of smooth muscle calponin in tumor vessels of human hepatocellular carcinoma and its possible association with prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a vascular-rich tumor. The tumor vessels in HCC were demonstrated to have alpha-smooth muscle actin positive smooth muscle cells (SMCs). However, it is unclear whether the SMCs in the wall of the tumor vessels are differentiated or undifferentiated. Basic calponin is an actin-, tropomyosin-, and calmodulin-binding protein, and expression of the calponin gene in SMCs has been recognized as one of the late stage differentiation markers of SMCs. The authors investigated the differentiation state of SMCs in tumor vessels by immunohistochemical examination of calponin in patients with HCC, and whether it is associated with the patients' prognosis. METHODS: Tumor and nontumor tissues were obtained from 75 patients with HCC who underwent radical hepatic resection. The differentiation state of the smooth muscle cells were evaluated based on the expression level of calponin, an actin-binding protein, using immunohistochemistry and reverse transcription-polymerase chain reaction analysis. The disease free survival (DFS) rates were estimated according to the Kaplan-Meier method comparing groups of patients with calponin positive and negative tumor vessels. A multivariate analysis based on the Cox proportional hazards regression model was performed to estimate whether the expression of calponin is an independent prognostic factor. RESULTS: In the 75 patients with HCC examined, 36 patients (48%) possessed calponin positive SMCs, and the remaining 39 (52%) did not. There were no significant differences in either clinical or pathologic factors between the two groups of patients. The 5- and 8-year DFS rate of the patients with calponin positive vessels were 37% and 26%, respectively. These values were significantly higher (11% and 5%) than those of patients with calponin negative vessels. Gender, TNM classification, perioperative transfusion, and calponin expression were found to be independent prognostic factors for DFS. CONCLUSIONS: Immunohistochemical examination of the calponin expression in the tumor vessels is a new and useful means to predict the prognosis of HCC patients after hepatic resection.

Aged↗

Cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers.

BACKGROUND: Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. MATERIALS AND METHODS: Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining. RESULTS: CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860). CONCLUSIONS: Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.

Esophageal Neoplasms↗

Functions of the stratum corneum in systemic sclerosis as distinct from hypertrophic scar and keloid functions.

Both transepidermal water loss (TEWL) and skin surface high-frequency conductance are functions of the skin barrier. Systemic sclerosis (SSc) and hypertrophic scar (HS)/keloid are characterized by abnormal fibrotic changes in the dermis. Since the close interrelationship between the epidermis and the dermis has been well established, we analyzed the stratum corneum functions of forearm skin in 39 SSc patients after assessing the degree of the skin thickening and compared those functions with 10 age-matched normal controls. We also analyzed the stratum corneum functions of HS or keloid lesions in seven patients using the same methods, and compared those functions to adjacent or contralateral normal skin in identical patients. Neither the TEWL, nor high-frequency conductance of forearm skin in SSc patients were significantly different from those in normal controls. There was no correlation between the levels of TEWL or high-frequency conductance and the degree of skin thickening in SSc. In HS or keloid conditions, high-frequency conductance was significantly elevated (42.5+/-8.9 vs. 26.4+/-5.7, P<0.001). Although TEWL was elevated, there was no statistical significance (48.6+/-39.7 vs. 25.1+/-10.1). Our results revealed that stratum corneum functions are distinct between SSc and HS or keloid. This may reflect the various natures of dermal changes, which in turn differentiate the functions of the stratum corneum in the diseases.

Adult↗

Hyaluronan synthase 3 regulates hyaluronan synthesis in cultured human keratinocytes.

Three human hyaluronan synthase genes (HAS1, HAS2, and HAS3) have been cloned, but the functional differences between these HAS genes remains obscure. The purpose of this study was to examine which of the HAS genes are selectively regulated in epidermis. We examined the relation of changes between hyaluronan production and HAS gene expression when cytokines were added to cultured human keratinocytes. Interferon-gamma increased hyaluronan production whereas transforming growth factor beta decreased it. Both cytokines affected preferentially high-molecular-mass (> 106 Da) hyaluronan production. Consistent with the change in hyaluronan synthesis, we found that interferon-gamma markedly upregulated HAS3 mRNA whereas transforming growth factor beta downregulated HAS3 transcript levels. The expression of HAS1 mRNA was not significantly affected by either cytokine, and HAS2 mRNA expression was undetectable under either basal or cytokine-stimulated conditions by northern blot using total RNA. Furthermore, in situ mRNA hybridization showed that mouse epidermal keratinocytes abundantly expressed HAS3 mRNA from the basal to the granular cell layers, suggesting that HAS3 functions in epidermis. These findings suggest that HAS3 gene expression plays a crucial role in the regulation of hyaluronan synthesis in the epidermis.

Animals↗

Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after resection of an intraductal papillary-mucinous carcinoma of the pancreatic head: a case report and comparison of DNA sequence in K-ras gene mutation.

Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.

Adenocarcinoma, Mucinous↗

Main pancreatic duct dilatation: a sign of high risk for pancreatic cancer.

BACKGROUND: The prognosis of pancreatic ductal adenocarcinoma remains very poor, but is better in patients with a small tumor without local infiltration. The identification of the sign of high risk for pancreatic cancer will lead to early detection and improvement of the prognosis of this disease. The purpose of this study was to evaluate the main pancreatic duct dilatation as a sign of high risk for pancreatic cancer. METHODS: The diameter of the main pancreatic duct was measured by ultrasonography. The proportion of cases with main pancreatic duct dilatation was retrospectively examined in a pre-cancer group (39 subjects in whom pancreatic cancer developed more than 1 year later and surgically resected) and in a control group (10 244 subjects). Then the proportions in both groups were compared using the odds ratio. RESULTS: The proportion of cases with a slight dilatation (>/=2 mm in diameter) of the main pancreatic duct was 65% in the pre-cancer group, more than 4 years before the resection of the pancreatic cancer. In contrast, it was 5.35% in the age-matched control subjects. The odds ratio of 32.5 (95% confidence interval: 10.9-107.3) shows a significant association between the main pancreatic duct dilatation and the pre-cancer condition. Moreover, the proportion and the mean diameter of the dilated duct in the pre-cancer group increased with time. CONCLUSION: Slight dilatation of the main pancreatic duct appears to be a sign of high risk for pancreatic cancer. The systematic examination of high-risk subjects is recommended for the early detection of pancreatic cancer.

Adolescent↗

A case of hypersensitivity syndrome due to phenytoin.

We report a 30-year-old female with hypersensitivity syndrome (HS) due to phenytoin. Her disease course was typical with elevation of the antibody titer for human herpes virus 6. Three courses of methylpredonisolone pulse therapy were required to control the disease activity. Since the pathogenic mechanism and treatments for HS have not been established, further clinical analyses are warranted.

Adult↗