[Histochemical observation using thrombomodulin staining method for damage of sinusoidal endothelial cells: preliminary report].
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Animals↗
Biomedical subjects
H Shimazu
Publications and source records attributed to H Shimazu.
[A basic study on usefulness of bleomycin incorporated in poly DL-lactic acid].
Poly DL-lactic acid (PLA) is one of the biodegradable polymers. Bleomycin (BLM) incorporated into small cylinders of PLA blends was prepared as a new dosage (BLM-PLA). When BLM-PLA was preserved in saline, the dissolution rate of BLM from BLM-PLA was 49.2% after 7 days, 85.2% after 14 days and 99.7% after 21 days, respectively. BLM-PLA was implanted subcutaneously into the back of 36 rats. On days 3, 7, 14, 21, 28 and 35, the connective tissues near the implants, lymph node, lung, liver and kidney were removed and BLM activity was measured. The BLM concentration was maintained at a high level in the connective tissues until 14 days, and in the lymph node between 21 and 28 days. On the other hand, the BLM level was low in the lung, liver and kidney. Consequently, it was suggested that PLA is useful as a carrier for drug delivery system and that administration of BLM-PLA is an effective anti-cancer modality, especially in local chemotherapy.
Animals↗
Uptake of bleomycin adsorbed on to activated carbon particles by regional lymph nodes of the esophagus in dogs.
Two bleomycin (BLM)-containing agents (BLM-CH, BLM-SOL) were prepared, and the possible usefulness of BLM-CH in the targeting of chemotherapy for esophageal cancer was studied. BLM-CH is an agent in which BLM is adsorbed on to activated carbon particles, and BLM-SOL is an aqueous solution of BLM. BLM-CH or BLM-SOL was injected into the submucosa of the middle thoracic esophagus of 14 mongrel dogs under endoscopic control. Three days after the administration, regional lymph nodes, connective tissues, liver, lung and spleen were removed, and BLM in the specimens was measured. When BLM-CH was administered, BLM was demonstrated not only in the lymph nodes near the injection site but also in the cervical and abdominal ones. In contrast, BLM was not detected in any lymph nodes when BLM-SOL was administered. Light and electron microscopic observation showed that activated carbon particles diffused and were distributed in the lymph nodes. The latter findings also revealed their existence in the interstices of lymphatic tissues and macrophages. When BLM-CH was injected, BLM in the blood was significantly lower when compared with the results of BLM-SOL administration. The results obtained indicate that BLM-CH may probably become a useful tool in targeting chemotherapy for esophageal cancer.
Adsorption↗
[A case of postoperative chylothorax successfully treated by chemical pleurodesis with OK-432].
Recently, cases of postoperative chylothorax have increased concomitantly with the increase in number of aggressive thoracic surgery. Chylothorax was complicated on the 6 th postoperative day in a 69-year-old male who underwent right lower lobectomy with mediastinal lymph node dissection for adenocarcinoma of the lung. After the leaking point from thoracic duct was confirmed by lymphangiography and chest CT, OK-432 1.5 KE was instilled into the intrapleural space through a intrathoracic tube. By this procedure, the chylous fistulas were completely cured. Application of OK-432, even in such a small dose as 1.5 KE, appeared very useful for the treatment of postoperative chylothorax.
Adenocarcinoma↗
[A case of chondrosarcoma of the thoracic vertebra].
A case of chondrosarcoma of the thoracic vertebra in a 47-year-old female is described. Chest X-ray, CT and MRI disclosed an abnormal mass lesion in the posterior mediastinum. The lesion was surgically removed through right thoracotomy. The operative findings revealed that the lesion, hard and measuring 6.5 x 4.5 x 4.5 cm in diameter, was originated from the 7th and 8th thoracic vertebra. The lesion was histopathologically diagnosed chondrosarcoma. The chondrosarcoma arising from the thoracic vertebra is very rare, and only 10 cases have hitherto been reported in the Japanese literature.
Chondrosarcoma↗
Effect of a dihydropyridine analogue, 2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo- 1,3,2-dioxaphosphorinan-2-yl)-1-(2-morpholinoethyl)-4-(3-nitrophenyl)-3 -pyridinecarboxylate on reversing in vivo resistance of tumor cells to adriamycin.
A newly synthesized dihydropyridine analogue, 2-[benzyl(phenyl)-amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-1- (2-morpholinoethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate (PAK-200), at 5 microM inhibited the efflux of [3H]vincristine from KB-C2 cells and increased the accumulation of [3H]vincristine in KB-C2 cells to a level similar to that in KB-3-1 cells. PAK-200 inhibited the photoaffinity labeling of P-glycoprotein in KB-C2 membranes by [3H]azidopine. At 5 microM, PAK-200 enhanced the cytotoxic effect of Adriamycin on drug-sensitive KB-3-1 cells, multidrug-resistant KB-8-5 cells, and two human colorectal carcinoma tumor lines, COK-28LN and COK-36LN, by factors of 2, 5, 2, and 3 times, respectively. The calcium antagonistic activity of PAK-200 was about 1000 and 5 times lower than that of another dihydropyridine analogue, nicardipine, and of verapamil, respectively. PAK-200 in combination with Adriamycin completely suppressed the growth of KB-3-1 and COK-36LN and partially suppressed the growth of KB-8-5 but had no significant effect on COK-28LN cells xenografted in nude mice. The level of MDR1 expression of COK-36LN was about 3 times higher than that of COK-28LN, but lower than that of KB-8-5 cells. These results suggest that the interaction of PAK-200 with P-glycoprotein may be partly correlated with the enhancement of the antitumor effect of Adriamycin on xenografted KB-8-5 and COK-36LN cells in nude mice.
Animals↗
Vestibular and visual interaction in generation of rapid eye movements.
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Animals↗
Carbohydrate profiles shown by a lectin and a monoclonal antibody correlate with metastatic potential and prognosis of human lung carcinomas.
The expression of two carbohydrate markers--namely, 4C9 antigen, which is an Lex antigen, and the Dolichos biflorus agglutinin (DBA) binding site, which is an N-acetylgalactosamine marker--was examined histochemically in tumors and adjacent nontumorous tissues of 102 cases of human lung carcinomas. In nontumorous tissues, the DBA binding site was expressed more frequently than 4C9 antigen, and the DBA binding site had a tendency to be expressed more significantly than in tumor cells. Adenocarcinomas and well-differentiated tumors had a tendency to more cell surface staining. Patients with tumors that expressed DBA binding sites but not 4C9 antigen (4C9-, DBA+) had fewer metastasis and significantly better prognoses than patients with tumors of other carbohydrate profiles. Better prognosis of patients with 4C9-, DBA+ tumors was observed in those with blood group A antigen and those without it, and the better prognosis also was observed in patients with Stage I and IIIA disease.
Adolescent↗
Rapid and marked induction of hepatocyte growth factor during liver regeneration after ischemic or crush injury.
Liver injuries induced by ischemia or physical trauma are characterized by noninflammatory damage frequently observed in a clinical setting. When the liver of rats was injured by ischemic treatment or physical crushing, necrotic tissue degeneration occurred in several sites of lobulus within 24 hr. Hepatocyte growth factor, a potent mitogen for adult rat hepatocytes in primary culture, was markedly induced in the livers of rats injured by ischemia or physical trauma. In both cases, the hepatocyte growth factor messenger RNA level in the injured liver reached about 10 to 20 times that of the normal level during 12 to 24 hr after liver injury. The increase in hepatocyte growth factor messenger RNA correlated well with the degree of liver damage as evaluated by serum ALT activity in the sera of rats. In situ hybridization showed that hepatocyte growth factor messenger RNA expression occurs in nonparenchymal liver cells, primarily in Kupffer cells of the ischemic liver. After the increase of hepatocyte growth factor messenger RNA in the injured liver, a marked compensatory hepatocyte DNA synthesis occurred 48 to 72 hr after these treatments. These results suggest that hepatocyte growth factor acts as a hepatotropic factor for liver regeneration after noninflammatory liver damage caused by ischemia and physical crush, probably through a paracrine mechanism.
Animals↗
A correlation between arterial ketone body ratio and concentration of beta-hydroxybutyrate as an indicator of hepatic functional reserve.
We have investigated the correlation between the arterial blood ketone body ratio (AKBR) and beta-hydroxybutyric acid (HBAC) in the course of a 75 g glucose tolerance test. The correlation was revealed to be represented by an equation of Y = A + BX [X = log(HBAC), Y = log(AKBR)] with high significance. This expression existed in both normal individuals and patients with liver, biliary tract or pancreas disease. The postoperative course was unsatisfactory because of liver dysfunction in cases whose value B was more than -0.6 in bisegmentectomy and more than -0.45 in uni- or subsegmentectomy. The coefficient B in the equation was suggested to contribute to the evaluation of hepatic functional reserve.
3-Hydroxybutyric Acid↗
Monoclonal antibodies against a human gastric cancer cell line with lung metastatic potential in nude mice define antigens with different expression between the primary and metastatic liver lesions.
SCK-29 is a tumor cell line derived from human gastric adenocarcinoma with the feature of producing lung metastases when xenografted in nude mice. Monoclonal antibodies were produced against SCK-29 tumor cells or their glycoproteins prepared by affinity chromatography on a lectin-agarose column. Five antigens defined by the monoclonal antibodies MG-1 to MG-5 were expressed in a large number of gastric or colonic adenocarcinomas. Among the antigens, MG-1 and MG-3 proved to be tumor-associated, since they were detected only occasionally in normal tissues. MG-5 antigen was often detected in normal gastric mucosa but not in other tissues. The degree of expression of MG-1. MG-3 and MG-5 antigens differed considerably in metastatic lesions. In metastatic liver lesions of gastric adenocarcinoma, expression of these MG antigens was less marked than in primary tumors. MG-1 and MG-3 antigens were abolished by neuraminidase digestion and periodate oxidation. MG-5 antigen was likely to be a protein antigen, since it was resistant to neuraminidase digestion and to periodate oxidation but was sensitive to protease digestion.
Adenocarcinoma↗
Endorectal ultrasonography for the assessment of wall invasion and lymph node metastasis in rectal cancer.
Endorectal ultrasonography (ERUS) with a flexible-type radial scanner (Aloka Co. Ltd., Tokyo, Japan; 7.5 MHz) was applied to 120 patients with rectal cancer for the assessment of wall invasion and pararectal lymph node metastasis. Normal rectal wall was described as a five- or seven-layer structure excluding the lowest part within 3 cm from the anal verge. Loss of normal layers basically indicated the existence of cancer invasion. According to UICC classification, we divided the depth of wall invasion into four ultrasonographic levels (uT1-uT4), and results were correlated with histopathologic findings. Overall accuracy of the assessment was 92.0 percent (103/112). Overestimation occurred in 5 of 60 cases with T3 cancer (8.3 percent), and underestimation occurred in 1 of 19 cases with T2 cancer (5.3 percent) and 3 of 60 cases with T3 cancer (5 percent). Inflammatory cell infiltration was found around the cancer in a considerable number of cases. However, the assessment of wall invasion was hardly affected in our hands. Because the muscularis propria of the rectal wall was often recognized as a three-layer structure, uT2 cancer was subdivided into three subgroups of uPM1, uPM2, and uPM3. The assessment of invasion of sublayers in muscularis propria was possible in 14 of 19 cases (73.7 percent), and correct assessment was achieved in 57 percent of the cases. The ultrasonographic demonstration of pararectal lymph nodes was studied on 98 patients. No swollen lymph nodes were detected ultrasonographically in 35 of 98 cases (35.7 percent), but cancer metastasis was found histopathologically in 5 of these 35 cases (14.3 percent). The metastasis was observed more frequently in lymph nodes with a diameter of more than 5 mm (53.8 percent) and in those with a well-defined boundary and with an uneven and markedly hypoechoic pattern (72.3 percent). Although unable to detect minimal cancer foci. ERUS was considered a very useful tool for the assessment of the depth of cancer invasion in the rectal wall and pararectal lymph node metastasis.
Humans↗
Early postoperative chemotherapy following noncurative resection for patients with advanced gastric cancer.
We studied the effect of early postoperative chemotherapy, including 5-fluorouracil (5-FU) for 5 days for patients with gastric cancer following noncurative resection. The study was prospectively randomised and controlled, and 162 (87.1%) of 186 were eligible candidates for statistical assessment. Patients randomised to group A received therapy that is used widely to treat patients with gastric cancer in Japan; mitomycin C (MMC), OK-432, UFT and PSK. Patients randomised to group B received the same drugs given to group A plus 5-FU bolus injections for 5 days, beginning on postoperative day 2. There were no differences in prognostic factors and doses of the drugs prescribed, except for 5-FU. There was no difference in the toxicity rate between the groups. Generalised Wilcoxon test revealed a P value of 0.169, and the 50% survival rate improved 1.4-fold in patients with gastric cancer treated with early postoperative chemotherapy of MMC, OK-432 plus 5-FU injection.
Aged↗
A novel core protein as well as polymorphic epithelial mucin carry peanut agglutinin binding sites in human gastric carcinoma cells: sequence analysis and examination of gene expression.
The peanut agglutinin (PNA)-binding site is protein-bound Gal beta 1-->3GalNAc, and is a tumor-associated carbohydrate marker expressed in many human carcinomas. PNA-binding glycoproteins isolated from KATO-III human gastric carcinoma cells were deglycosylated by trifluoromethanesulfonic acid, and rabbit antibodies against the core proteins were used to screen a lambda gt11 expression library constructed from these cells. Two different core proteins were identified by this approach. One was polymorphic epithelial mucin (PEM), initially found in breast carcinomas. PEM mRNA was expressed in normal tissues of the stomach, colon, and lung, but not in the small intestine, thyroid, and spleen. High levels of PEM mRNA were detected in some nude mouse-transplanted carcinomas, i.e. colorectal, pancreatic, stomach, and lung carcinomas. The other core protein was a novel one called MGC-24, which has a molecular mass of 24 kDa, is rich in hydroxyl amino acids and cysteine, and lacks repeating motifs. The mature MGC-24 glycoprotein behaved as a high-molecular-mass one upon SDS-polyacrylamide gel electrophoresis even after neuraminidase treatment. Treatment with endo-alpha-N-acetylgalactosaminidase in the absence of neuraminidase significantly changed the staining pattern by anti-MGC-24, confirming that MGC-24 carried PNA-binding sites. MGC-24 mRNA was intensely expressed in normal tissues of the colon, small intestine and thyroid, and in some nude mouse-transplanted colorectal and pancreatic adenocarcinomas.
Amino Acid Sequence↗
[A case of hepatoma patient who showed an abnormally high level of serum IRI with the beads method].
A fifty four years old hepatoma patient admitted to the hospital for a surgical operation. Preoperative laboratory examination demonstrated that his serum IRI level was very high (423 microU/ml) when measured with a beads method, however RIA or a microplate method demonstrated normal values. We studied the mechanism of the discrepancy of IRI values. 1) Both the beads and microplate methods demonstrated the same IRI values when the patient's serum insulin was roughly purified with Sep-Pak. The beads method showed high IRI values in serum which passed through Sep-Pak, therefore contained no insulin. 2) The similar results were observed when the patient's serum fractionated by a gel-chromatography (Biogel P-30). The beads method demonstrated high IRI values in both insulin fractions and the fractions containing serum proteins bigger than 40,000 molecular weight. The microplate method demonstrated only one large peak of insulin. 3) When non-specific IgG of guinea pig was used as a fixed antibody instead of human insulin antibody of guinea pig that was used in the beads method, the patient's serum showed the similar values as that obtained with the beads method. We thereby concluded that the abnormal level of IRI by the beads method was derived from the unknown substance reacting with IgG of guinea pig in the patient's serum. After the surgical resection of hepatoma, the levels of IRI measured by the beads method decreased significantly, suggesting that the substance is related to hepatoma cells.
Animals↗
[Postoperative changes in acute phase protein in patients with esophageal cancer].
Thirty-three patients with esophageal cancer were studied to assess the relationship between nutritional state and the acute phase protein responses. Blood samples taken preoperatively and days 1, 4, 7 and 14 after operation were analyzed for C-reactive protein, fibrinogen, alpha 1-antitrypsin, alpha 1-acid glycoprotein and haptoglobin. Significant Spearman's coefficients were found between percent of ideal body weight (IBW) and alpha 1-acid glycoprotein (r = -0.42), between prealbumin and alpha 1-anti-trypsin (r = -0.55), and between retinol-binding protein and alpha 1-antitrypsin (r = -0.51). Postoperatively, the levels of C-reactive protein, fibrinogen, alpha 1-anti-trypsin and alpha 1-acid glycoprotein were significantly lower in the poorly nourished group than in the other groups. The changes of acute phase proteins in the immediate postoperative period were affected by the preoperative nutritional state, and were less marked in the poorly nourished patients. Between two groups of patients in whom lymph node dissection was carried out in 2 or 3 areas, no significant differences were observed in the acute phase protein responses postoperatively. The measurement of acute phase proteins is very important in assessing the body defense capacity of the patient, but it should be noted that the changes may be affected by several factors including malnutrition.
Acute-Phase Proteins↗
[Evaluation of nutritional status in patients with esophageal cancer by measurement of sternocleidomastoid, rectus abdominis and quadriceps muscles on ultrasound imaging].
To assess the nutritional status of the patients with esophageal cancer, we measured the areas of sternocleidomastoid and rectus abdominis muscles (SMA, RAMA) on real time ultrasound imaging and calculated muscle index (MI = (SMA+RAMA/Height)). Eighty-three patients with esophageal cancer were included in the present study. Preoperatively, significant Spearman's coefficients were found between MI and the percentage of standard arm circumference (R = 0.52) and between MI and the percentage of standard arm muscle circumference (R = 0.51). Postoperatively, patients with wide muscle area showed high values of prealbumin, transferrin and fibronectin. To study the changes after surgery, we also measured the area of quadriceps muscle in patients with esophageal cancer. The areas of quadriceps muscle in patients with dysphagia were much diminished than in those without dysphagia. Measurement of areas of muscles such as SMA, RAMA and quadriceps muscle was proved to be a useful procedure in evaluating the nutritional status of patients with esophageal cancer.
Abdominal Muscles↗
[A successfully treated case of thoracic meningocele with von Recklinghausen's disease].
Intrathoracic meningocele is an uncommon disease. Only 95 cases in the foreign literature and 13 cases in Japanese literature have been reported since Phol Meningocele occurs most frequently in the sacral and lumbar spinal regions. In this present paper, an 18-year-old female with intrathoracic meningocele associated with neurofibromatosis is described. The patient was admitted to our Surgical Clinic with a complaint of constrictive pain in the upper chest. The meningocele was diagnosed preoperatively and resected surgically by left thoracotomy. The patient has been followed up to for six years without any evidences of local recurrence. However, she recently complains of headache and weakened eyesight because of pituitary tumor, the operative indication of which is now discussed.
Adolescent↗