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Biomedical subjects

C Sakamoto

Publications and source records attributed to C Sakamoto.

At least 37 records · Page 2Linked to original sources

Risk of colorectal cancer in patients with hematologic disease.

BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.

Aged↗

Relationship between cyclooxygenase-2 expression and K-ras gene mutation in colorectal adenomas.

BACKGROUND AND AIMS: Cyclooxygenase (COX)-2 has a trophic effect on gastrointestinal epithelial cells and is associated with the progression of colorectal adenomas. Mutation of the K-ras gene is also associated with the progression of colorectal adenomas and has recently been suggested to play an important role in the induction of COX-2. In the present study, we investigated the relationship between COX-2 expression and K-ras mutation in colorectal adenomas. METHODS: Twenty-nine colorectal adenomas were obtained from specimens resected by the use of surgery or endoscopic mucosal resection and analyzed clinicopathologically. Immunohistochemistry was performed to analyze COX-2 expression in the adenoma specimens. The K-ras codon 12 mutations were detected by using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: An increase of COX-2-positive cells in adenoma was observed in 11 (37.9%) lesions, 10 (90.9%) of which had a K-ras gene mutation, suggesting a significant correlation between COX-2 expression and K-ras gene mutation in colorectal adenomas. Morphologically, COX-2-positive adenomas (13.8 +/- 2.6 mm) were significantly larger than COX-2-negative ones (5.8 +/- 0.9 mm). In addition, the increase of COX-2-positive cells in the lesion was observed more frequently in tubulovillous (63.6%) than in tubular (36.4%) adenoma. CONCLUSIONS: Cycloxygenase-2 expression in colorectal adenoma cells is strongly correlated with K-ras gene mutation, suggesting that COX-2 and mutated K-ras are connectively associated with the progression of colorectal adenoma.

Adenoma↗

A novel epidermal growth factor-like molecule containing two follistatin modules stimulates tyrosine phosphorylation of erbB-4 in MKN28 gastric cancer cells.

We have isolated a gene from stomach fibroblasts encoding novel proteins containing two follistatin modules which might bind TGF-beta-related growth factors and a single epidermal growth factor (EGF)-like domain which is closely related to EGF/Neuregulin (NRG) family growth factors. Sequence analysis revealed novel cDNA clones, the protein products of which were designated tomoregulin (TR) and consisted of at least three isoforms which were distinguished by their cytoplasmic domains. The cytoplasmic domains in all isoforms were short and contained potential G-protein activating motifs. Precursors of TR (Pro-TR) are glycosylated transmembrane proteins. Two secreted soluble forms resulting from proteolytic cleavage were distinguished by the presence or absence of the EGF-like domain. The EGF-like domain of TR was highly conserved compared to EGF/NRG family growth factors with the exception of an arginine to histidine substitution at position 39 (Arg --> His 39). Soluble TR stimulated erbB-4 tyrosine phosphorylation in MKN 28 gastric cancer cells, although it was weak compared to neuregulin-induced erbB-4 tyrosine phosphorylation; this suggests that TR might be a ligand for erbB-4- or erbB-4-related receptor tyrosine kinase. TR may have important roles in normal development of middle to late stages of embryos and maintenance of adult central nervous system tissues as high expression of TR mRNAs was observed in these tissues. The modular features suggest multiple roles for TR; these include functioning as a ligand for erbB- receptor, a regulator of TGF-beta-related growth factor signaling by direct interaction through the follistatin modules, and a G-protein-coupled receptor.

Amino Acid Sequence↗

Expression of heregulin alpha, erbB2, and erbB3 and their influences on proliferation of gastric epithelial cells.

BACKGROUND & AIMS: Heregulins (HRGs) regulate the proliferation and differentiation of various cell types. However, very little is known about their function in the gastrointestinal tract. The aim of this study was to investigate the role of HRGs on gastrointestinal cells. METHODS: We examined the expression of erbB receptors and HRG-alpha in human gastric cancer cell lines, rat gastrointestinal epithelial cells, and human gastric fibroblasts by Western blot analysis or reverse-transcription polymerase chain reaction. Receptor phosphorylation and heterodimerization induced by HRG-alpha were detected by Western blot analysis. We also evaluated the in vitro effects of HRG-alpha on cell proliferation and restitution. RESULTS: Cancer cell lines and rat epithelial cells expressed erbB2 and erbB3, but protein expression of erbB4 was not detected. HRG-alpha was detected only in gastric fibroblasts. HRG-alpha activated tyrosine phosphorylation of epidermal growth factor receptor (EGFR), erbB2, and erbB3 and induced not only erbB3/erbB2 but also erbB3/EGFR and erbB2/EGFR heterodimer formation in MKN-28 cancer cells. Simultaneous cultivation of MKN-28 cells with gastric fibroblasts resulted in tyrosine phosphorylation of erbB3 in MKN-28 cells. HRG-alpha also stimulated proliferation of MKN-28 cells and gastric epithelial cells. CONCLUSIONS: The data suggest that HRG-alpha may affect epithelial cell proliferation through mesenchymal-epithelial interaction in the gastric mucosa.

Animals↗

Evaluation of a new laboratory test measuring plasma (1-->3)-beta-D-glucan in the diagnosis of Candida deep mycosis: comparison with a serologic test.

We evaluated the effectiveness of the newly developed WAKO beta-glucan test which measures plasma (1-->3)-beta-D-glucan concentrations in the diagnosis of Candida deep mycosis. This test was compared to the Cand-Tec test. The WAKO beta-glucan test and Cand-Tec test were performed on 212 plasma specimens which were taken at 212 instances from 62 immunocompromised patients with serious diseases; i.e. hematopoietic malignancy, solid malignant tumor, etc. The sensitivities and specificities for the WAKO beta-glucan test were 84.8 and 85.9%, respectively, and 60.9 and 80.0% for the Cand-Tec test.

Candidiasis↗

Automated enumeration of cellular composition in bone marrow aspirate with the CELL-DYN 4000 automated hematology analyzer.

The present study was designed to evaluate the automated analysis of bone marrow aspirates with the CELL-DYN 4000 (CD4000) hematology analyzer. Bone marrow aspirates were diluted twice with phosphate-buffered saline and assayed with the CD4000. The percentages of subpopulations including lymphocytes, neutrophils, and erythroblasts were obtained with the CD4000, and as a reference, differential counts by microscopic observation of May-Grünwald-Giemsa-stained films of bone marrow aspirate were performed (n = 48). Significant correlations (p < 0.0001) between the results with the two methods were obtained for total nucleated cell count, lymphocytes, neutrophils, erythroid cells, and the myeloid/erythroid ratio. The present method can provide quantitative data of bone marrow aspirate and will be useful in bone marrow screening.

Biopsy, Needle↗

Purification and characterization of D-glucosaminitol dehydrogenase from Agrobacterium radiobacter.

D-Glucosaminitol dehydrogenase, which catalyzes the conversion of D-glucosaminitol to 3-keto-D-glucosaminitol, was purified to apparent homogeneity from extracts of Agrobacterium radiobacter. This organism has constitutively depressed levels of the enzyme but expression of the enzyme is induced by addition of D-glucosamine to the medium. Purification included ammonium sulfate fractionation and chromatography on columns of DEAE-Sephacel, Octyl-Sepharose CL-4B, and Cellulofine. The purified enzyme migrated as a single band, coinciding with dehydrogenase activities specific for D-glucosaminitol and ethanol, when electrophoresed on a 7.5% polyacrylamide gel at pH 8.0. Electrophoresis on a 12.5% PAGE in the presence of 1% SDS also yielded a single band. The enzyme had an apparent molecular mass of 79 kDa, as measured by the pattern of elution from a column of Cellulofine. The results indicated that the enzyme was a dimer of identical (or nearly identical) subunits of 39.5 kDa. D-Glucosaminitol dehydrogenase required NAD+ as a cofactor and used ethanol as the preferred substrate, as well as aliphatic alcohols with 2 to 4 carbon atoms, D-glucosaminitol, D-glucosaminate, DL-allothreonine, glycerol, and erythritol as additional substrates. In 50 mM Tris-HCl buffer (pH 9.0) at 25 degrees C, the K(m) for D-glucosaminitol, ethanol, and NAD+ were 2.2, 2.0, and 0.08 mM, respectively. The enzyme had a pH optimum of 10 for D-glucosaminitol and 8.5 for ethanol. The enzyme lost substantial activity when treated with pyrazole, with certain reagents that react with sulfhydryl groups and with Zn2+ ion. The various results together suggest that the enzyme exploits different amino acid residues for the dehydrogenation of ethanol and of D-glucosaminitol.

Amino Acid Sequence↗

Roles of COX-1 and COX-2 in gastrointestinal pathophysiology.

In this review, COX-1 and COX-2 proteins have been shown to be homologous in protein structure and ability to synthesize PG, but they have been also shown to be induced differently. COX-1 mRNA and protein have been shown to be induced slowly in intestinal crypt cells in response to irradiation and suggested to be important for crypt cell survival. Therefore, the cox-1 gene is suggested to be a delayed response gene in some systems. However, in cox-1 gene knockout animals there are no pathological gastric and intestinal findings. Although the precise roles of COX-1 in epithelial proliferation and differentiation in the gastrointestinal tract are not yet known, it apparently acts as a constitutive PG producer, thereby protecting the mucosa. On the other hand, COX-2 mRNA and protein have been shown to be induced rapidly in inflammatory sites of the stomach and colon. Thus, COX-2-derived PG presumably plays a role in the repair process of gastritis, ulcers, and colitis. Furthermore, loss of apc gene function probably induces COX-2 mRNA in gastrointestinal mucosa. Thus, high expression levels of COX-2 may lead to phenotypic changes in both intestinal epithelial cells and colon cancer cells.

Cloning, Molecular↗

[Treatment of hepatosplenic candidiasis with liposomal amphotericin B in a patient with acute leukemia; a case report of the experience of use of liposomal amphotericin B].

We report a 26-year-old male patient with acute myelocytic leukemia and hepatosplenic candidiasis during his clinical course. His hepatosplenic candidiasis was refractoty to itraconazole and fluconazol. He developed serious side-effect such as renal dysfunction, when conventional amphotericin B was given. Then he was treated with liposomal amphotericin B (Abelcet). This therapy was safe and effective for him. He was able to be treated with 3075 mg of a liposomal amphotericin B. This was ten times as much as the dose of conventional amphotericin B which was given earlier until amphotericin B was stopped because of renal dysfunction. Liposomal amphotericin B seems to be a safe and effective therapy for systemic fungal infectin and should be considered more in Japan.

Adult↗

Gastric epithelial cells secrete a PDGF-like peptide, a potent mitogen for human gastric fibroblasts.

To investigate whether gastric epithelial cells secrete growth factors involved in stromal cell growth, we examined the effects of conditioned media obtained from gastric cancer cells on murine BALB/c 3T3 cells and primary cultured human gastric fibroblasts. Conditioned media from MKN-1 gastric cancer cells were applied to a heparin-affinity column. The fraction eluted from the column at 0.4 M NaCl stimulated DNA synthesis and phosphorylation of PDGF alpha-receptors on tyrosine in BALB/c 3T3 cells. The fraction-induced stimulation of DNA synthesis in gastric fibroblasts was more marked than in BALB/c 3T3 cells. However, the fraction failed to stimulate DNA synthesis in CHO-ER cells overexpressing EGF receptors and phosphorylation of PDGF beta-receptors on tyrosine in BALB/c 3T3 cells. Immunoblot analysis of the media confirmed that PDGF-AA-like peptides are released from gastric cancer cells, immortalized gastric epithelial cells, and primary cultured gastric epithelial cells. Anti-PDGF neutralizing antibodies produced only a partial inhibition of 0.4 M NaCl fraction-induced enhanced DNA synthesis. Thus, in addition to PDGF-AA peptide, other bioactive substance(s) are probably released from MKN-1 gastric cancer cells. Our results suggest that gastric epithelial cells secrete PDGF-AA-like peptides responsible for stromal cell growth through paracrine mechanisms.

3T3 Cells↗

[Factitious anemia with severe iron deficiency caused by self-venesection].

A 22-year-old unmarried female student of nurse school was admitted to our hospital because of hypochromic anemia and fever of unknown origin. She was diagnosed as having iron-deficiency anemia and was treated with iron, but progressive anemia recurred periodically. In particular, rapidly progressive anemia was observed after the patient stayed overnight, so we strongly suspected factitious anemia. A search of her locker in the sickroom and her room at home revealed many syringes, injection needles and a bottle of blood. Factitious anemia was diagnosed and she confessed to self blood-drawing. After a psychiatric consultation, anemia tended to to resolve gradually. However she did not go to the hospital after 6 months from her discharge. Physicians should consider factitious anemia in a patient with severe chronic hypochromic anemia who dose not respond to adequate iron therapy, particularly in a patient with medical training.

Adult↗

Comparison of the mechanisms of latency shift in pattern reversal visual evoked potential induced by blurring and contrast reduction.

Reduction of visual acuity or of the contrast of the stimulus induces a prolongation of the pattern reversal visual evoked potential (PR-VEP) latencies, perhaps because these conditions cause deterioration of the visual capacity to recognize objects and may preferentially activate the slower central retina channel. The PR-VEP was obtained with a video stimulator and 3 kinds of stimuli: total video field, video with a central scotoma and a restricted central stimulus. The subjects were tested under conditions of normal (20/20) and reduced visual acuity (20/200) with 14' and 56' checks and 60% contrast, and under conditions of normal visual acuity (20/20) with 14' checks and with stimulus contrast of 60% and 25%. Blurring increased latencies and decreased amplitudes only with the 14' checks stimulus but no with 56' checks, and the amplitudes obtained with the central stimulus became greater than those obtained with a central scotoma. Reducing contrast increased only latency, and there was not difference between amplitudes obtained with a central stimulus or a central scotoma. We conclude that blurring small checks induces a preferential stimulation of receptors in the central retina, but the same effect was not observed when stimulus contrast was reduced.

Adult↗

Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice.

BACKGROUND & AIMS: The role of two forms of cyclooxygenase (COX-1 and COX-2) in gastric mucosal lesions is not well understood. The regulation of both forms of COX and the effect of COX-2 on the repair process of gastric mucosal lesions in mice were investigated. METHODS: Gastric mucosal erosions and ulcers were induced experimentally in mice. The level of COX messenger RNA (mRNA) was determined by reverse-transcription polymerase chain reaction. COX proteins were detected by Western blot analysis, and COX activity was determined in the presence or absence of NS-398, a specific COX-2 antagonist. The effects of long-term administration of NS-398 on gastric ulcers were examined. RESULTS: COX-2 mRNA levels were not detected in control conditions but were high during the acute stages of gastric erosions and ulcers. COX-2 protein was detected 5 days after ulcer induction but not in control mice. Gastric ulceration was not associated with a change in COX-1 mRNA and protein levels. Administration of NS-398 to mice with ulcers at acute stages impaired the healing of ulcers. CONCLUSIONS: High levels of COX-2 mRNA and protein during the acute stages of gastric mucosal lesions may be involved in the repair process of these lesions in mice.

Acetic Acid↗