Successful simultaneously stapled lobectomy for a stab wound to the lung with massive hemorrhage: case report.
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Adult↗
Biomedical subjects
T Aoki
Publications and source records attributed to T Aoki.
Cloning and functional expression of a cytochrome P450 cDNA encoding 2-hydroxyisoflavanone synthase involved in biosynthesis of the isoflavonoid skeleton in licorice.
Isoflavonoids are distributed predominantly in leguminous plants and play critical roles in plant physiology. A cytochrome P450 (P450), 2-hydroxyisoflavanone synthase, is the key enzyme in their biosynthesis. In cultured licorice (Glycyrrhiza echinata L., Fabaceae) cells, the production of both an isoflavonoid-derived phytoalexin (medicarpin) and a retrochalcone (echinatin) is rapidly induced upon elicitation. In this study, we obtained a full-length P450 cDNA, CYP Ge-8 (CYP93C2), from the cDNA library of elicited G. echinata cells. When the flavanones liquiritigenin and naringenin were incubated with the recombinant yeast microsome expressing CYP93C2, major products emerged and were readily converted to the isoflavones daidzein and genistein by acid treatment. The chemical structures of the products from liquiritigenin (2-hydroxyisoflavanone and isoflavone) were confirmed by mass spectrometry. CYP93C2 was thus shown to encode 2-hydroxyisoflavanone synthase, which catalyzes the hydroxylation associated with 1,2-aryl migration of flavanones. Northern-blot analysis revealed that transcripts of CYP93C2, in addition to those of other P450s involved in phenylpropanoid/flavonoid pathways, transiently accumulate upon elicitation.
Amino Acid Sequence↗
An immunohistochemical study of E-cadherin expression in human squamous cell carcinoma of the skin: relationship between decreased expression of E-cadherin in the primary lesion and regional lymph node metastasis.
E-cadherin is a Ca(2+)-dependent, intercellular adhesion molecule that is specifically expressed in epithelial tissues and is essential for maintaining intercellular connections. It has been reported that E-cadherin expression of tumor cells is often decreased in some types of metastasizing carcinomas as compared with those without metastasis. We immunohistochemically examined the expression of E-cadherin with anti-E-cadherin monoclonal antibody and compared primary lesions of human squamous cell carcinoma of the skin (SCC) with regional lymph node metastasis to those without regional lymph node metastasis. Tumor samples from fifty-five cases of SCC (32 cases of SCC without metastasis and 23 cases with metastasis) were formalin-fixed, paraffin-embedded, and examined. E-cadherin was reduced or absent in 39 (70.9%) out of 55 cases of SCC, and in 21 (91.3%) of 23 cases with regional lymph node metastasis. Our results suggest that the decreased expression of E-cadherin in the primary lesion is correlated with regional lymph node metastasis in SCC and that it is more frequently correlated with well-differentiated than with poorly differentiated SCC. E-cadherin may be useful as a marker for metastatic potential in well-differentiated SCC.
3,3'-Diaminobenzidine↗
Shedding of membrane type 1 matrix metalloproteinase in a human breast carcinoma cell line.
Membrane type 1 matrix metalloproteinase (MT1-MMP) with a transmembrane domain is a new member of the MMP gene family and is expressed on the cell surfaces of many carcinoma cells to activate the zymogen of MMP-2 (gelatinase A). We have previously reported that MT1-MMP is released into culture media in a complex form with tissue inhibitor of metalloproteinases 2 (TIMP-2) from a human breast carcinoma cell line, MDA-MB-231, treated with concanavalin A (Con A). In the present study, we further studied the release mechanism of MT1-MMP. Immunoblot analysis indicated that the amounts of MT1-MMP in culture media increase with the time of exposure and the concentration of Con A, and those in cell lysates conversely decrease in a similar way. Time- and dose-dependent release of MT1-MMP into the media was confirmed by a sandwich enzyme immunoassay specific to MT1-MMP. The molecular weight of the immunoreactive MTI-MMP in the media was Mr 56,000, which was 4,000-Mr smaller than that in the cell lysates. Northern blot analysis demonstrated that the mRNA expression level of MT1-MMP is about 3-fold enhanced after a 24 h-exposure to Con A and this is maintained up to 72-h exposure. The release of MT1-MMP from the Con A-treated cells was inhibited by metalloproteinase inhibitors such as EDTA and o-phenanthroline, but not by MMP inhibitors including TIMP-1, TIMP-2 and BB94 or other proteinase inhibitors of serine, cysteine and aspartic proteinases. During the Con A treatment of the cells, cell viability decreased time- and dose-dependently and dead cells reacted positively in the TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Con A-treated MDA cells showed apoptotic morphology when stained with Hoechst dye and hematoxylin and eosin. DNA ladder formation was detected by electrophoresis of the DNA from Con A-treated MDA cells. These results suggest that MT1-MMP release from Con A-treated cells is due to shedding mediated by metalloproteinase(s) other than MMPs, and is associated with apoptosis.
Apoptosis↗
A case of granulocyte-colony stimulating factor producing gallbladder cancer.
Ever since the identification of the colony-stimulating factor (CSF), granulocyte-CSF (G-CSF)-producing tumors have often been reported, and have been attracting attention, especially in pulmonary cancer. However, there have been only a small number of reports of G-CSF-producing tumors in cases of gastrointestinal cancer, and only four cases of G-CSF-producing gallbladder cancer have been reported so far. Recently, we encountered a 73-yr-old man with G-CSF-producing gallbladder cancer. The leukocyte count in the peripheral blood increased to the maximum of 75,200/mm3 during the course of observation, and mature neutrophils accounted for 97% (segmented forms: 89%, band forms: 8%). The serum G-CSF concentration was high (129 pg/ml). The leukocyte count became normalized postoperatively, and the serum G-CSF concentration also decreased (50 pg/ml). The tumor was diagnosed as undifferentiated adenocarcinoma of the pleomorphic type on the histopathologic examination. Numerous tumor cells were stained with the anti-G-CSF antibody. Detailed findings of the patient are presented here together with some discussion of the literature.
Adenocarcinoma↗
Incomplete Sjögren-Larsson syndrome in two Japanese siblings.
Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder characterized by ichthyosis, spastic diplegia and mental retardation. Biochemical studies have pinpointed the pathogenesis resulting in the deficiency of the fatty aldehyde dehydrogenase (FALDH) component of the fatty alcohol NAD+ oxidoreductase complex. Histochemical analysis revealed a reduction in alcohol dehydrogenase (AD) activity in the skin. SLS patients have been categorized biochemically into two groups: complete and incomplete reduction according to the degree of FALDH deficiency. Our patients demonstrated incomplete clinical features, including a 1/3 reduction in FALDH activity, and decreased AD activity in the ichthyotic lesion. The phenotypical differences between our cases and classic SLS are probably due to the partial FALDH deficiency.
Aldehyde Oxidoreductases↗
Threshold concentration of unbound bilirubin to induce neurological deficits in a patient with type I Crigler-Najjar syndrome.
Based on the clinical course of a 16-year-old boy with type I Crigler-Najjar syndrome, we estimated the threshold concentration of unbound bilirubin, as assayed by the horseradish peroxidase method, that apparently induces toxicity to the brain. Before the age of 15, the patient did not manifest any neurological or behavioural dysfunction despite increased bilirubin in serum. The binding affinity and the binding capacity of the patient's serum albumin for bilirubin determined when he was about 14 years old were 10(8)(mol/L)-1 and 1.01 to 1.04 mol/L, respectively. These values were nearly the same as those of normal controls reported in the literature. The total bilirubin binding capacity was greater than the patient's total bilirubin concentration, showing that his serum albumin was not saturated with bilirubin. The reserve bilirubin binding capacity (RBBC) was estimated to be 158 mumol/L and the unbound bilirubin concentration to be 15.1 nmol/L. Concentration of unbound bilirubin peaked at 21.7 nmol/L at the age of 15 years and 11 months, i.e. 2 months before the onset of difficulties in walking and speaking. At this time, the RBBC was estimated as -64 mumol/L. A peak concentration of total bilirubin, 811 mumol/L, was observed during the period of rapid loss of the ability to walk or speak. At the age of 16 years and 1 month the RBBC decreased to -98 mumol/L and the unbound bilirubin concentration to 18.8 nmol/L. Following phototherapy, the patient's neurological state returned to normal; he could speak and walk normally. At the age of 16 years and 2 months the RBBC returned to 105 mumol/L and unbound bilirubin decreased to 16.6 nmol/L. These results suggest that maintaining the concentration of unbound bilirubin at < 20 nmol/L and the total bilirubin concentration at lower than the binding capacity of serum albumin is important for prevention of neurological deficits in Crigler-Najjar syndrome. The upper limit of unbound bilirubin in such an older patient was nearly the same as that reported for newborns.
Adolescent↗
A milk clotting assay for antibody using a fusion protein between protein A and pepsinogen C.
The proteolytic activity of a fusion protein between protein A and human pepsinogen C (PA-PGC) was measured by a modified milk clotting assay on 96-well microtiter plate. The assay ranges for 30 and 120 min-incubation were approximately 0.08-1.25 ng and 0.02-0.16 ng, respectively. Although the absorbance of milk solution decreased by the precipitation of clotted casein, the white precipitate was, if anything, convenient for an easy detection of reaction-positive wells. The borderline between the wells with or without precipitate was very clear and easily detected without the plate reader. This feature was thought to be suitable for the positive-negative judgment of a dilution test in enzyme immunoassay (EIA). Rabbit IgG adsorbed on a microtiter plate was then measured using PA-PGC and this milk assay (designated as PA-PGC assay). Although PA-PGC assay needed slightly longer incubation than the conventional color assay, the sensitivity of both systems was almost identical, and the reaction-positive wells containing white precipitate were easily detected at a very low range by the over night incubation without using the plate reader. PA-PGC assay possesses the unique and useful properties, and it can be used as a convenient and easy EIA technique.
Animals↗
Acute pan-costochondritis demonstrated by gallium scintigraphy.
Costochondral inflammation is a rare clinical finding. A case is presented, in which acute chostochondritis is demonstrated by gallium scinitigraphy.
Acute Disease↗
Induction of isoflavonoid and retrochalcone branches of the flavonoid pathway in cultured Glycyrrhiza echinata cells treated with yeast extract.
Yeast extract-treated suspension cultures of a new cell line, AK-1, of Glycyrrhiza echinata were induced to produce an isoflavonoid phytoalexin (medicarpin) and metabolites of retrochalcone/flavone pathway (echinatin, licodione, and 7,4'-dihydroxyflavone). From these cells, putative full-length cDNAs encoding cytochrome P450s, (2S)-flavanone 2-hydroxylase and isoflavone 2'-hydroxylase, were cloned.
Cloning, Molecular↗
CT-guided agar marking for localization of nonpalpable peripheral pulmonary lesions.
BACKGROUND: Small pulmonary lesions with ground-glass opacity (GGO) are increasingly detected by CT; however, intraoperative localization of such lesions is difficult because these lesions are often invisible and nonpalpable. STUDY OBJECTIVES: To localize and resect nonpalpable and invisible small pulmonary lesions, a new marking technique that we call "agar marking" was developed. METHODS AND PATIENTS: Powdered agar was dissolved in distilled water at a concentration of 5% and kept at > 50 degrees C to maintain its liquid form. Agar was injected through an 18-gauge needle and placed near the target lesion with CT. After animal experiments, agar marking was applied to the nine patients who had lesions < 20 mm in diameter and lesions with GGO. The mean diameter of these lesions was 11 mm, with a mean depth of 19 mm from the pleural surface on CT. RESULTS: Agar could be detected as a hard nodule by manual palpation, and the lesion was resected during thoracotomy in all cases. There were no complications associated with the agar injection, aside from one case of slight pneumothorax. CONCLUSIONS: Agar marking may represent a feasible alternative technique for localizing nonpalpable occult lesions located away from the pleural surface.
Agar↗
Toxicological response of rats to a novel monoamine oxidase type-A inhibitor, (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5- methoxymethyl-2-oxazolidinone (E2011), orally administered for 13 weeks.
(5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5- methoxymethyl-2-oxazolidinone (E2011) is a novel monoamine oxidase type-A (MAO-A) inhibitor. In order to assess toxicological profiles of E2011, doses of 0 (as controls), 30, 100 mg/kg of E2011 were administered to male and female Sprague-Dawley rats once a day for 13 weeks orally by gavage. No mortality or any toxic signs except salivation occurred due to E2011 treatment. Decreased body weight gain and food consumption, increases of alkaline phosphatase and increases of liver weight were the major treatment-related findings observed predominantly in the 100 mg/kg group. Histological examination revealed nuclear enlargement of hepatocytes with appearance of altered cell foci in some cases, and acinar atrophy in Harderian glands in the 100 mg/kg group. Since the histopathological findings in the liver were indicative of an ongoing carcinogenic process, glutathione S-transferase placental form (GST-P) positive hepatic foci were identified immunohistochemically and examined morphometrically. Although GST-P positive hepatic foci were detected in all groups including controls, the number and area of GST-P positive hepatic foci were significantly higher in female rats treated with 100 mg/kg than those in controls. In this paper, possible mechanisms of specific lesions in the liver and Harderian glands will be discussed.
Administration, Oral↗
[General toxicity study of gadobenate dimeglumine formulation (E7155) (3)--4-week repeated dose intravenous toxicity study followed by 4-week recovery period in rats].
A 4-week repeated dose toxicity study of gadobenate dimeglumine formulation (E7155) was conducted in Sprague-Dawley rats to assess its non-clinical safety. E7155 was administered intravenously at doses of 0.3, 1.0 and 3.0 mmol/kg/day to male and female rats once a day during 4 weeks. The reversibility of toxicity was evaluated during a 4-week recovery period at 3.0 mmol/kg/day. At 0.3 mmol/kg/day and higher, vacuolation of the cortical epithelium was seen in the kidneys and an increase in the incidence of local damage at the injection sites. In the 1.0 and 3.0 mmol/kg/day male and female groups, scabbing/ulceration of the tail at the injection sites, macroscopic pale/thickened fundic mucosa in the stomachs, vacuolation of the urinary bladder, and mucosal mineralization with epithelial hyperplasia of the glandular stomach were found. In the 1.0 and 3.0 mmol/kg/day male group and 3.0 mmol/kg/day female group, increases of water consumption and urinary potassium excretion, increased kidney weight and enlargement of the kidneys were observed. In the 3.0 mmol/kg/day male and female group, hepatocyte necrosis with inflammatory cells in the liver and epithelial degranulation in the interlobular ducts of the salivary glands were found. In addition, in the 3.0 mmol/kg/day male group, increases in plasma sodium and decreases of urinary sodium and chloride excretion, and degenerative changes in the testes and epididymides were observed. After the 4-week recovery period, except for an increase in urinary potassium excretion, increased kidney weights and changes in the testes and epididymides, all of the above findings had complete or partial recovery. Vacuolation of renal tubular cells was common, expected, and known as an adaptive change of treatment with hypertonic solutions, and an increase in the incidence of local damage at the injection sites was due to irritation by repeated intravenous dosing with hypertonic solutions. Therefore, these changes were not toxic changes. In conclusion, the dose level of 0.3 mmol/kg/day should be regarded as the No Observed Adverse Effect Level (NOAEL) after repeated administration of E7155 in rats.
Animals↗
Bioavailability of milk micellar calcium phosphate-phosphopeptide complex in rats.
We evaluated the bioavailability of two types of calcium from milk in two experiments. One was a micellar calcium phosphate-phosphopeptide (MCP-PP) complex in which the chemical form was similar to the original form of milk, and the other was a commercial whey calcium in which the chemical form was different from that of milk. In experiment 1, the calcium absorption, bone mineral density, and bone strength were examined when growing female rats were fed either MCP-PP complex or whey calcium as the sole source of calcium for 46 d. In experiment 2, the calcium solubility in the small intestine was measured when female rats were meal-fed either MCP-PP complex or whey calcium. The apparent calcium absorption rate in both groups decreased time-dependently during the experimental period, but the time-dependent change in the apparent calcium absorption rate was statistically different. It decreased more slowly in rats fed the MCP-PP diet than in rats fed the whey calcium diet. The bone mineral density of the femur in rats fed the MCP-PP diet was significantly higher than that of the rats fed the whey calcium diet. The bone strength (breaking force and energy) of the femur in rats fed the MCP-PP diet was higher than in the rats fed the whey calcium diet. The amount of soluble calcium in the small intestinal contents in rats at 2.5 h after ingestion of the MCP-PP diet was approximately three times higher than that found in rats fed the whey calcium diet. These results indicate that the calcium bioavailability of MCP-PP complex is higher than that of whey calcium, and this difference is due in part to the solubility in the intestine.
Absorption↗
Identification of a 5-cM region of common allelic loss on 8p12-p21 in human breast cancer and genomic analysis of the hEXT1L/EXTR1/EXTL3 gene in this locus.
The short arm of chromosome 8 is frequently lost in many human carcinomas including breast cancer, suggesting the presence of a tumor suppressor gene(s) in this region. We identified a gene termed hEXT1L/EXTR1/EXTL3 (hEXT1L hereinafter) that was mapped to chromosome bands 8p12-p21 where frequent LOHs of this region was reported in breast cancer. The existence of the third breast cancer susceptibility gene was also suggested in this region by linkage analysis. We further performed LOH analysis in 8p12-p21 in 34 breast cancers and identified a 5-cM region of common allelic loss that overlapped with the locus for positive lod score in familial breast cancer. We further analyzed genomic alterations of hEXT1L in tumors in which frequent LOHs of 8p were reported. A total of 327 cancers (313 primary tumors and 14 cancer cell lines) including 22 primary breast cancers were analyzed, but none of the tumors had somatic mutations: only one thyroid cancer patient without any family history of cancer had a 9-bp insertion in the constitutional DNA. These results suggest that mutations of hEXT1L do not play a major role in the development of sporadic cancers including breast cancer, and that other tumor suppressor gene(s) exists in the 5-cM region identified in this study.
Alleles↗
Multiple extra-bone accumulations of technetium-99m-HMDP.
Bone scintigraphy was performed on a woman 2 y and 10 mo after surgery for rectal cancer. Intense extra-bone accumulations of 99mTc-HMDP were visible in an aortic atherosclerosis lesion and in a metastatic liver tumor. Uptake in the metastatic lesion was confirmed by x-ray CT. Uptake in the aortic lesion was shown as typical calcification by x-ray CT.
Aged↗
[A study of hypertriglyceridemia occurring in patients with chronic hepatitis C during administration of interferon beta].
The prevalence and risk factors of hypertriglyceridemia during the administration of interferon (IFN) were examined in 78 patients with chronic hepatitis C who were treated with 6 MU of IFN-beta once or 3 MU of IFN-beta twice a day for 6 weeks. Hypertriglyceridemia (serum triglyceride (TG) above 150 mg/dl) was found before the start of IFN treatment in 9% of the patients. During the administration of IFN, elevation of serum TG above 150 mg/dl was found in 82% of patients. In addition, serum TG level exceeded 500 mg/dl at least once during the administration of IFN in 13% of patients. On stepwise multiple regression analysis, three risk factors, high serum TG value before the administration of IFN, high ALT value before the administration of IFN, and divided administration of IFN-beta twice daily were found to be associated with hypertriglyceridemia during IFN administration.
Adult↗