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Biomedical subjects

O Ishikawa

Publications and source records attributed to O Ishikawa.

At least 145 records · Page 8Linked to original sources

X-linked dominant chondrodysplasia punctata with decreased dihydroxyacetone phosphate acyltransferase activity.

BACKGROUND: We examined an 18-month-old girl with typical clinical features of X-linked dominant chondrodysplasia punctata (CDPX2) with decreased activity of dihydroxyacetone phosphate acyltransferase (DHAP-AT), previously reported in CDPX2. On the other hand, steroid sulfatase, whose activity is deficient or decreased in X-linked ichthyosis and X-linked recessive chondrodysplasia punctata, has been reported to be normal in CDPX2, although all of these diseases have ichthyotic skin changes. OBJECTIVE: We measured the activity of DHAP-AT and steroid sulfatase of the patients fibroblasts to confirm the DHAP-AT abnormality in CDPX2. RESULTS: The DHAP-AT activity was remarkably reduced, but steroid sulfatase activity was within normal levels when compared with those of 2 healthy controls. CONCLUSION: The abnormal metabolism in plasmalogen synthesis in CDPX2 was confirmed. It is, however, unknown how the decreased DHAP-AT activity is related to the skin changes.

Acyltransferases↗

Generalized morphea with vascular involvement. A case report and disaccharide analysis of the skin glycosaminoglycans.

We report a 69-year-old man with severe generalized morphea, who showed over 80% of skin involvement, while the internal organs were not affected. We performed histological examinations and analysis of skin disaccharides constituting chondroitinase-digestible glycosaminoglycans in the center and periphery of the sclerotic lesions and the clinically uninvolved skin. In both the central and peripheral parts of the sclerotic lesions, sclerotic fibrosis and a dense perivascular cell infiltration, consistent with morphea, were seen in the entire dermis and subcutis. Furthermore, various vascular changes were observed, such as endothelial cell swell, thickened basement membrane and obstruction of vascular lumen in the fat lobules. In the clinically uninvolved skin, interstitial edema was prominent along with a slight perivascular cell infiltration. On disaccharide analysis, the increase in the amount of delta Di-4S(DS), the main disaccharide unit of dermatan sulphate, delta Di-6S and delta Di-6S, the main disaccharide units of chondroitin sulphate, and the decrease in delta Di-HA, which is derived from hyaluronate, were found not only in the sclerotic lesions but also in the clinically uninvolved skin, though less prominent. These alterations were consistent with systemic sclerosis, suggesting a close relationship between severe forms of generalized morphea and systemic sclerosis.

Aged↗

Focal dermal hypoplasia (Goltz syndrome): a decreased accumulation of hyaluronic acid in three-dimensional culture.

We report a 28-year-old female with focal dermal hypoplasia, (Goltz syndrome). We compared the growth kinetics and the production of type I collagen and glycosaminoglycans by fibroblasts from affected and unaffected skin. Fibroblasts were grown in conventional medium supplemented with ascorbic acid 2-phosphate, which makes fibroblasts from a tissue-like structure in vitro. The population doubling time of fibroblasts in affected skin was slightly shorter than that of unaffected skin. There was no difference in the levels of the carboxyterminal propeptide of type I procollagen liberated into the media between affected skin and unaffected skin. However, the cell layer of affected skin fibroblasts revealed a decreased amount of hyaluronic acid-derived disaccharide unit (delta Di-HA). The abnormal metabolism of glycosaminoglycan in the affected dermis might be involved in the development of skin changes in focal dermal hypoplasia.

Adult↗

[Clinical value of carbohydrate antigens, sialyl Lewis-x and sialyl Lewis-a in gastrointestinal cancer].

To evaluate clinical importance of the expression of sialyl Lewis-X (sLe(x)) and sialyl Lewis-a antigen (sLe(a)) in gastrointestinal cancers, we examined immunohistochemically expression of the two antigens in esophageal, gastric, colorectal, and pancreatic cancer. Expression of sLe(x) and sLe(a) were associated with several clinicopathologic features which reflect tumor aggressiveness in esophageal, gastric and colorectal cancer, but not in pancreatic cancer. In esophageal and colorectal cancer, survival rate of the patients with sLe(x) positive tumors was significantly poorer than that of the patients with sLe(x) negative tumors, while in gastric cancer that with sLe(a) positive tumors was significantly poorer than that with sLe(a) negative. Cox's multivariate analysis revealed that sLe(x) expression status was one of the significant discriminants of prognosis in colorectal cancer patients and sLe(a) status in gastric cancer patients. These results suggest that sLe(x) and sLe(a) expression could be involved in aggressiveness of gastrointestinal cancer and might prove to be a potent marker for prognosis in patients with gastric cancer and colorectal cancer.

Adult↗

[Quick radioimmunoassay for plasma immunoreactive gastrin--application for localizing occult gastrinoma(s) during operation].

A rapid method for determining gastrin, quick gastrin, has been developed. Separation/washing procedure has been improved and can be completed within three minutes. It required only 48 minutes for the assay of 22 blood samples. Quick gastrin is a RIA that uses magnetic particles. On magnetic particles, a goat anti-rabbit IgG antibody is bound covalently. An anti-human gastrin rabbit antibody is bound to an anti-rabbit IgG antibody. Assay is started by adding the magnetic particles to a mixture of sample and 125I-gastrin. Following 30 minute incubation at 37 degrees C, the particles are sedimented in a magnetic field and washed. The gastrin content of the sample is then quantitated by counting radioactivity of the particles. Incomplete equilibration of antigen-antibody reaction is corrected using standard solution prepared from charcoal treated plasma. The immunoreactive gastrin values by quick gastrin correlated well with those by a commercial assay kit (Gammadab RIA kit; y = 1.01 x +4.3, r = 0.99). When compared to a reported conventional rapid assay, quick gastrin is easier and more accurate. Quick gastrin is sensitive enough to use for intra-operative determination of gastrin. We applied quick gastrin to the samples obtained from intra-operative secretin test in a gastrinoma patient. Twofold increases in gastrin after injection of secretin clearly indicated the existence of occult gastrinomas in her pancreas. When gastrin was assayed with the conventional rapid method, the increase in gastrin was less and did not reach the criteria for existence of gastrinoma.

Adult↗

[Adjuvant chemotherapy for advanced gastric cancer].

For recent 40 years, many authors reported the results of adjuvant chemotherapy for advanced gastric cancer including 5-fluorouracil, uracil and tegafur, mitomycin C, cytosine arabinoside. OK-432 adriamycin, methotrexate, and cis-pltatin in solitary use of combinations. It is difficult to find a standard effective adjuvant chemotherapy for advanced gastric cancer in these reports. The reasons of this unclearness were as follows; (1) In phase III studies, surgery alone was not a control group in some reports. (2) The number of patients was too small to evaluate statistically. (3) Inter-institutional differences had important roles in the results of multicenter study in the other studies. For the future plans on adjuvant chemotherapy, it is important to make a simple designed protocol, and perform it as a multicenter study including institutions with minimum inter-institutional differences.

Antineoplastic Combined Chemotherapy Protocols↗

Antineutrophil cytoplasmic autoantibodies in patients with systemic sclerosis.

Perinuclear type of antineutrophil cytoplasmic antibodies (p-ANCA) have been found in patients with periarteritis nodosa, Churg-Strauss arteritis, or pauci-immune idiopathic crescentic glomerulonephritis. Recently, the association of p-ANCA and normotensive renal failure, in patients with systemic sclerosis (SSc), was reported. We have studied the incidence of p-ANCA in patients with SSc and have investigated its relationship to clinical and laboratory findings. Sera from 77 patients with SSc were examined by the indirect immunofluorescence (IIF) test, employing an ethanol-fixed human neutrophil and enzyme-linked immunosorbent assay, using purified myeloperoxidase (MPO) as an antigen (MPO-ELISA). The sera from seven patients (9.1%) were p-ANCA positive, by both IIF and MPO-ELISA. One patient died from systemic necrotizing angiitis but the remaining six patients have shown no symptoms of systemic vasculitis or of renal involvement. There was a tendency for patients positive for p-ANCA (anti-MPO antibody) to also be positive for other autoantibodies, such as anti-Sc1-70 antibody, anti-centromere antibody, anti-microsome antibody, anti-thyroglobulin antibody and rheumatoid factor. Although the incidence of p-ANCA (anti-MPO antibody) is low in patients with SSc, and its clinical significance in SSc needs further investigations, this could be a serological marker for certain symptoms in SSc.

Antibodies, Antineutrophil Cytoplasmic↗

Membranocystic changes in the panniculitis of dermatomyositis.

Clinically apparent panniculitis is rare in dermatomyositis. The common histopathological findings are infiltration of lymphocytes, epithelioid cells and plasma cells in the fat lobules, along with varying degrees of fat degeneration and fibrosis. We report a 65-year-old woman with dermatomyositis who developed panniculitis with a characteristic histological change known as a membranocystic lesion. Although this change has been observed in various diseases affecting the subcutaneous fat tissue, it has rarely been reported in dermatomyositis. Dermatomyositis should be included in the diseases showing a membranocystic lesion.

Aged↗

Characteristics of histamine release from cultured human mast cells.

BACKGROUND: The mast cell is one of the important cells in the pathogenesis of allergic disorders. However, isolating human mast cells is a laborious procedure. Recently, cultured human mast cells raised from umbilical cord blood cells have become available. It is necessary to examine whether these cells are useful in investigating the role of mast cells in human diseases. OBJECTIVE: The phenotype of mast cells depends on their anatomical sites. To examine which phenotype of mast cells these cultured mast cells most closely resemble, their ability to release was investigated. METHODS: The mast cells were raised from human umbilical cord blood cells in the presence of stem cell factor and interleukin-6. To determine the mast cell subtypes, the mast cells were immunocytochemically stained for tryptase and chymase. The cultured mast cells were then stimulated with various secretagogues, and histamine release was measured by a fluorometric technique using high-performance liquid chromatography. RESULTS: The immunocytochemical staining for mast cell proteases revealed that virtually all cells contained tryptase, the definitive marker of mast cells, and that about a quarter of the cells contained chymase. Anti-IgE effectively stimulated these mast cells to release histamine in a dose-dependent, time-dependent manner. The release was completed in about 30 min. One of the non-specific stimuli, calcium ionophore A23187, also induced histamine release in a dose-dependent, time-dependent manner. In contrast, compound 48/80 and substance P failed to induce histamine release from these cells. CONCLUSION: Cultured human mast cells resemble lung mast cells in their ability to release histamine. They will help in studying the functional properties of human mast cells and may contribute to clarifying the pathophysiology of human allergic diseases.

Antibodies, Anti-Idiotypic↗

Flow cytometric DNA content analysis on squamous cell carcinomas according to the preceding lesions.

DNA-ploidy in primary cutaneous squamous cell carcinomas which had developed from different preceding clinical lesions was examined by flow cytometry using paraffin-embedded blocks. DNA-aneuploidy was detected in none of 15 squamous cell carcinomas arising from a burn scar. On the other hand, 12 of 26 squamous cell carcinomas arising from sun-damaged skin in the elderly, and two of four arising from chronic radiodermatitis, showed aneuploid patterns. A significantly higher incidence of DNA-aneuploidy was observed in squamous cell carcinomas arising from sun-damaged skin than those from a burn scar (P < 0.01); the mean diameter size of the former was significantly smaller than that of the latter (P < 0.0001). The mean age of patients with aneuploid tumours (74.2 +/- 9.2: years +/- standard deviation (SD)) was significantly higher than that with diploid tumours (64.1 +/- 13.8) (P < 0.01).

Aged↗

Diagnosis of pancreatic cancer by K-ras point mutation and cytology of pancreatic juice.

OBJECTIVES: Recently, it was reported that detection of K-ras point mutation at codon 12 in pancreatic juice is an objective method for the diagnosis of pancreatic cancer, but a few reports have suggested that this might represent an early event in pancreatic oncogenesis. In the present study we examined, in various patients, the occurrence of K-ras codon 12 point mutation in pancreatic juice and compared it with pancreatic juice cytology, which is also a reliable diagnostic method. METHODS: Pancreatic juice was obtained endoscopically from patients with various pancreatic disorders and those without definite diseases, and was examined cytologically and for the occurrence of K-ras codon 12 point mutation. The K-ras gene was amplified by polymerase chain reaction (PCR) and the mutation at codon 12 (GGT-->GAT) was examined by slot blot hybridization analysis. RESULTS: K-ras point mutation at codon 12 was detected in seven of 14 (50%) pancreatic cancers, in four of 10 (40%) mucin-producing tumors, in four of 13 (31%) chronic pancreatitis, and in two of 10 (20%) pancreas without definite disorders. K-ras point mutation was detected in nine of 18 (50%) pancreatic juice samples containing cancer cells, in eight of 18 (44%) pancreatic juice samples containing atypical cells, but in none of such samples containing only normal cells. CONCLUSION: Cancer cells were detected from pancreatic cancer exclusively, but K-ras point mutation at codon 12 was detected in pancreatic juice, not only from pancreatic cancer, but also from other diseases.

Aged↗

[Hepatic resection with "wrapping therapy" for advanced hepatocellular carcinoma uncontrolled by arterial embolization].

We report a 70-year-old male patient who had successful hepatic resection with "Wrapping therapy" for advanced hepatocellular carcinoma (HCC) uncontrolled by arterial embolization. His laboratory tests were as follows: Alb: 4.7 (g/dl), T. Bil:0.9 (mg/dl), ICG R15:26.8 (%), PT: > 100%, AFP:33 (ng/ml), HCV-Ab:(-), HBs-Ag:(-). Hepatic angiogram showed a 20 cm sized tumor in the left lobe and many large and small tumors in the right lobe. He received chemoembolization (TAE) five times during seven months. At the time of the fifth hepatic angiogram, TAE was assessed as ineffective because of the resulting collateral feeding arteries. Thus, he underwent left lobectomy, partial resection of the right lobe, and partial "Wrapping therapy" for the regions including foci supplied with parasitic branch. Afterwards, he had TAE two times. One year and five months after the procedure, he is still alive without signs of recurrence.

Aged↗

[A case of successful management of advanced cholangiocellular carcinoma by repeated hepatic resection].

A 50-year-old woman with advanced cholangiocellular carcinoma (CCC) underwent extended left hepatectomy and catheterization into the hepatic artery. Following the procedure, intra-arterial infusion chemotherapy of the fluorouracil (5-FU) was performed. This chemotherapy was given 13 times at 2,500 mg for 10 months, so the total dose of 5-FU was 32.5 g. About two years after the operation, the patient underwent hepatic resection again for solitary recurrence of CCC. The prognosis of CCC is very poor. Aggressive surgical resection may be the only method to assure a good outcome. However, the survival rate after curative resection has been low. Adjuvant hepatic arterial infusion chemotherapy after surgery may be effective for a good prognosis.

Antimetabolites, Antineoplastic↗

[A case of non-resectable pancreatic cancer surviving more than 4 years by intra-arterial infusion chemotherapy with angiotensin-II].

This is a report of a 62-year-old woman whose non-resectable pancreatic cancer had been treated effectively by a new method of intra-arterial regional chemotherapy for more than 4 years. A catheter was placed into the celiac artery during laparotomy, and an intra -arterial chemotherapy (methotrexate (50 mg) and Angiotensin-II (AT-II, 5 micrograms)) has been repeated every other week (108 times) in addition to the external beam therapy (50 Gy). Both pain relief and "partial response" in the size of tumor have been obtained, with no hepatic metastasis or adverse effect. She died of brain metastasis at 51 postoperative months. Autopsy revealed that the pancreatic tumor was mostly replaced by fibrous connective tissues. Scintigraphic study indicated that the intra-arterial infusion of AT-II increased the blood flow in the tumor but decreased it in the surrounding non-cancerous tissues. This seemed to explain the effective loco-regional control in the present case.

Angiotensin II↗

[Adjuvant therapies in combination with pancreatectomy for carcinoma of the pancreas].

In the treatment of adenocarcinoma of the pancreas, surgical resection is the only curative strategy. However, the long-term survival rate after pancreatectomy remains poor, and most patients died of loco-regional and/or hepatic recurrence. Thus, we should perform effective adjuvant therapies in combination with surgery, in order to completely prevent these two types of cancer relapse. The present article is designed to introduce the recent reports on the adjuvant chemo-and/or radio-therapies for this cancer. As for loco-regional control, extended pancreatectomy plus chemoradiation seems to be most promising, and preoperative chemoradiation will be more popular in the near future. In order to decrease hepatic metastasis, our "2-channel chemotherapy", a continuous infusion of 5-FU via both hepatic artery and portal vein, is very promising. If postoperative survival is improved by combining these two types of regional therapy, the role of pancreatectomy will be enlarged and more widely understood in the near future.

Adenocarcinoma↗

Enhancement of in vitro tumor-cell transcellular migration by tumor-cell-secreted endothelial-cell-retraction factor.

To investigate the factors affecting endothelial-cell retraction, we have studied the interaction of tumor cells with endothelial cells in 2 human pancreatic cancer cell lines, PSN-1 and MiaPaca-2. The extent of endothelial-cell retraction measured by the amount of intercellular junctional transport of FITC-dextran through an endothelial monolayer was increased by the addition of a conditioned medium (CM) from both cell lines, while CM from PSN-1 cells was 2 to 3 times more potent than that from MiaPaca-2 cells. After the treatment of endothelial monolayer with CM of PSN-1 cells, the ability of both PSN-1 cells and MiaPaca cells to adhere to or invade the monolayer increased. The addition of CM from PSN-1 cells did not affect the growth rate of either the endothelial or the tumor cells. The activity in the CM was heat-stable and bound to heparin-Sepharose, but was inactivated when treated by 0.5% trypsin. Protease inhibitors did not influence the activity. Pre-treatment of PSN-1 cells by an inhibitor of protein synthesis, cycloheximide, or of protein processing, benzyl-N-acetyl-alpha-D-galactosaminide, reduced endothelial-cell-retraction activity in the CM. The active substance in the CM fractionated in the molecular-weight range of 10,000 to 50,000. These results suggest that PSN-1 cells produce and secrete (a) soluble factor(s) that can induce endothelial-cell retraction, thus facilitating tumor-cell invasion.

Animals↗