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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 1,027 records · Page 57Linked to original sources

Pathogenic capacity of proteases from Serratia marcescens and Pseudomonas aeruginosa and their suppression by chicken egg white ovomacroglobulin.

The pathogenicities of three proteases from Serratia marcescens, two proteases from Pseudomonas aeruginosa, and one thermolysin from Bacillus stearothermophilus were examined. All proteases tested caused acute liquefactive necrosis of the cornea and descemetocele formation in guinea pig eyes after intrastromal injection, with the exception of the 60-kilodalton protease from S. marcescens, which produced only an opaque lesion. When injected into guinea pig skin, the protease also enhanced vascular permeability, which was followed by edema formation. The permeability-enhancing activity of the proteases increased in parallel with the concentration of the enzymes. When tested in vitro for its effect on these bacterial proteases, chicken egg white ovomacroglobulin (ovoM) inhibited the enzymatic activity of all the proteases after a short incubation period at an enzyme/inhibitor ratio (molar) of 1:1 to 1:4 or at a lower concentration after a longer incubation period. Such treatment of the proteases with chicken egg white ovoM before injection intrastromally into the eyes or intradermally into the clipped flanks of guinea pigs protected the cornea from destruction or completely prevented the permeability reaction and edema formation. No inhibitory effects of plasma protease inhibitors against these bacterial proteases were noted. Since the proteases are critical in the pathogenic processes caused by the bacteria, these results suggest a beneficial effect of ovoM against bacterial infections.

Animals↗

High-attenuation recent thrombus of the portal vein: CT demonstration and clinical significance.

Attenuation characteristics of portal vein thrombi on nonenhanced computed tomographic (CT) scans were assessed in 122 patients with proved portal vein thrombosis. Portal vein thrombi of high attenuation were found in four patients with hepatocellular carcinoma. From pathologic and radiologic studies, it was concluded that the high attenuation was caused by blood clots of recent onset formed at the tip of tumor thrombus. Differentiation from choledocholithiasis, hematobilia, and calcification of thrombi could be easily made by means of ultrasonography (US). Although plain CT is usually considered noncontributory in the diagnosis of venous thrombosis, it enabled the differentiation of recent thrombus in these four patients. Tumor thrombus in the major branches or main trunk of the portal vein is indicative of poor prognosis. When hepatic mass and high-attenuation portal vein thrombi are demonstrated with plain CT and substantiated by US, enhanced CT and angiography may be unnecessary for treatment of patients with advanced hepatocellular carcinoma.

Aged↗

Selective inhibition of erythropoiesis by sera from patients with chronic renal failure.

The pathogenesis of anemia in patients with chronic renal failure was studied by analyzing the effect of uremic sera on the in vitro colony growth of erythroid (CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. Uremic sera from 20 of 30 patients inhibited erythroid colony growth below 70% of control even when cultured with normal human bone marrow of the same blood type. On the other hand, only one of the sera inhibited colony growth of CFU-GM as compared with normal sera. On Sephadex G-15 gel filtration, the CFU-E-inhibiting activity appeared in two different fractions: the void volume peak and the delayed eluant before the second peak. The inhibiting activity in the former fraction was noted only in uremic sera. The results of this study suggest the existence of a serum inhibitor(s) of erythropoiesis with a relative molecular mass of more than 1500 Da which are virtually impossible to dialyze by conventional membranes.

Anemia↗

CP-54,883 a novel chlorine-containing polyether antibiotic produced by a new species of Actinomadura: taxonomy of the producing culture, fermentation, physico-chemical and biological properties of the antibiotic.

The novel chlorine-containing acidic polycyclic ether antibiotic CP-54,883 (C41H62O12Cl2) [corrected] is produced by the fermentation of Actinomadura routienii Huang sp. nov. This report presents the taxonomy and the fermentation conditions for the antibiotic-producing culture. The antibiotic is mainly active against Gram-positive bacteria. It protects chickens against Eimeria challenge in vivo and enhances rumen propionic acid in vitro. The physico-chemical properties are also characterized.

Animals↗

[Acute right ventricular infarction: assessment with radionuclide ventriculography].

The clinical significance of right ventricular (RV) infarction has been neglected compared with left ventricular infarction. In recent years, however, the clinical importance of RV function in the treatment of myocardial infarction has been well recognized. We performed prospective radionuclide studies to assess the incidence and prognosis of RV infarction in 50 cases of initial acute myocardial infarction (25 cases of anterior and 25 of inferior infarction). Radionuclide ventriculography was performed within the first two days after onset of symptoms, and repeated one-two weeks and one month after the attack, respectively. RV infarction was diagnosed by the presence of severe RV regional wall motion abnormalities and positive signs of at least one of the following diagnostic signs: ST elevation at V4R in the ECG, positive 99m-technetium pyrophosphate myocardial scintigram at the RV free wall, and positive right heart catheterization findings. Results were as follows: 1. RV infarction was documented in 15 of 25 cases with inferior infarction, but there were no cases in anterior infarction. 2. There were no remarkable changes of RV ejection fraction (EF) in anterior myocardial infarction during one month (41% +/- 8% in acute phase and 43 +/- 8% in four weeks later). However, RVEF was markedly improved from 34 +/- 11% during first two days, to 38 +/- 7% during one-two weeks, and 39 +/- 8% four weeks after the attack, in cases of inferior infarction with RV infarction. Without RV infarction, RVEF in cases of inferior infarction did not show improvement. 3. In 11 of 15 cases with RV infarction, RV regional wall motion abnormalities improved to the normal range, which seemed to contribute to the improvement of RVEF. 4. Hemodynamic findings with Swan-Ganz catheters showed typical findings compatible with RV infarction only in seven of 13 cases with RV infarction. Thus this finding implies that RV failure did not always accompany RV infarction. 5. Coronary arteriography revealed that right coronary arterial lesions proximal to the RV branch were documented in all 10 cases with RV infarction who had coronary arteriography. RV infarction, caused by deranged coronary blood flow at the RV branch of the right coronary artery, showed marked improvement of RVEF during four weeks after the attack in prospective radionuclide studies. This finding was not seen in left ventricular infarction. The pathophysiological mechanism of improvement of RVEF in RV infarction would be the difference of its coronary circulation compared with that of the left ventricle.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Catheterization↗

[General mechanism of intratumor accumulation of macromolecules: advantage of macromolecular therapeutics].

Selective tumor targeting of anticancer agents is critically important in cancer chemotherapy. We previously found that a polymer-conjugated anticancer protein (neocarzinostatin; NCS), named smancs, accumulated more in tumor tissues than did NCS. In order to determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins with various molecular sizes (12-160 kDa) and other properties. In addition, we used dye-complexed serum albumin to visualize its accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of the mice, and a ratio of the protein concentration in the tumor to that in the blood (T/B) of 5 was readily obtained within 6-48 h. A large protein like IgG required a longer time (72 h) to reach this value of 5. A T/B value of neither 1 nor 5 was achieved at a significant concentration with NCS, a representative small protein (12 kDa), at any time. We speculate that the tumoritropic accumulation of these proteins occurred because of hypervasculature and enhanced vascular permeability to even macromolecules, with little recovery through either blood vessels or lymphatic vessels from the tumor tissue. This accumulation of macromolecules in the tumor was also found after intravenous injection of dye (Evans blue) which was bound mostly to albumin. Thus, the albumin-dye complex was retained only in the tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. When this complex prepared in vitro was injected into the tumor and normal tissue, the latter tissue cleared it completely within 48 h whereas the tumor tissue retained most of it. The difference between the clearance from the tumor and that from normal tissue was based on the difference in lymphatic drainage of the two tissues. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis. We propose this general mechanism of the behavior of macromolecules and lipids as EPR (enhanced permeability and retention) effect in solid tumor at microvasculature level.

Animals↗

[Tumor growth inhibitory effects of SMANCS, a poly (styrene-maleic acid) conjugated derivative of neocarzinostatin, on various tissue culture cells].

Growth inhibitory effects of neocarzinostatin (NCS), and its conjugated derivative with poly (styrene-maleic acid), SMANCS, were examined on various tissue culture cells consisting of 13 lymphatic and 7 non-lymphatic cells (15 cell lines, 5 primary culture cells; 14 in suspension culture cells, 6 in monolayer cells). Both agents showed almost similar concentrations for the growth inhibition against 5 non-lymphatic cell lines (an average minimum growth inhibitory concentration of NCS, 0.076 microgram/ml, and SMANCS, 0.094 microgram/ml, a ratio of 1 : 1.24 (W/W), or 1.0 : 0.9 (mol/mol]. However, SMANCS showed a much less growth inhibitory effects against lymphatic 10 cell lines than NCS. Namely, an average 50% growth inhibitory concentration of NCS was 0.019 microgram/ml whereas that of SMANCS was 0.091 microgram/ml (a ratio of 1 : 4.79). From the consideration of each molecular weight, this ratio is 1 : 3.6. Similar results were obtained in experiments in which 2 primary non-lymphatic cells and 3 primary lymphatic cells were used. Although the largest drawback with NCS was known to be leukopenia, present results indicated the less toxicity of SMANCS than NCS on lymphatic cells and may provide a positive aspect of the new derivative, such as less incidence of leukopenia.

Animals↗

Facilitated internalization of neocarzinostatin and its lipophilic polymer conjugate, SMANCS, into cytosol in acidic pH.

The effects of environmental pH on the binding and cytotoxicity of the antitumor proteins neocarzinostatin (NCS) and SMANCS [copoly(styrene-maleic acid)-conjugated NCS] to cultured cells were studied by using their fluorescent-labeled derivatives (F-drugs). At 37 degrees C the binding of these drugs to HeLa cells was pH dependent: The amount of cell-bound drugs increased with an increase in the acidity of the medium. The pH-dependent change in the binding of the drugs was not as evident at 0 degree C. The cytotoxic action of these drugs was much more rapid at acidic pH compared with that at neutral or slightly alkaline pH. Furthermore, F-drugs could be utilized to probe the microenvironmental pH in Meth-A cells, in which the drug was located by the ratio of fluorescent intensities at 450 and 490 nm. The environment of the cell-bound F-drugs became acidic with incubation time at 37 degrees C but not at 0 degree C. Inasmuch as these drugs directly attack DNA, these results suggest that NCS and SMANCS are translocated across the membrane of acidic vesicles into the cytosol after endocytotic uptake. This hypothesis is also supported by the finding that NH4Cl and chloroquine protected HeLa cells against the cytotoxicity of the drugs. Data also showed that the hydrophobic polyanion conjugate SMANCS had a much greater cell binding (10 times) and more rapid internalization compared with NCS. Taken together, our results show that acidic pH of tumor tissue is preferable for effective binding and internalization into cytosol for NCS and SMANCS.

Ammonium Chloride↗

Cell surface phenotyping of megakaryoblasts.

Surface phenotypic characterization of megakaryoblasts, identified by platelet peroxidase activity, was investigated in four patients who showed increased proliferation of megakaryoblasts: one patient with typical features of acute leukemia, one presenting with acute myelofibrosis, and two with Down's syndrome in whom blasts disappeared spontaneously (transient abnormal myelopoiesis, TAM). MY10 and/or MY9 antigens were expressed on the surface of some megakaryoblasts, but MY7, and MY4, antigens specific to granulocytic or monocytic cells, were not. Some megakaryoblasts were positive for only anti-HLA-DR antibodies. It was speculated that, during the differentiation of the megakaryocytic lineage, MY9 antigen appears transiently on the surface of megakaryoblasts that have lost HLA-DR antigens and have gained the glycoprotein IIb/IIIa antigen. This study also demonstrated that the proliferating blasts in some patients with TAM were mainly megakaryoblasts and suggested that the target cells in TAM are CFU-GEMM.

Adolescent↗

[Prevention of hepatic metastases in rabbits by administration of an oily anticancer agent into the portal vein].

We studied one kind of prophylactic chemotherapy against hepatic metastases. The therapy was carried out with a lymphographic oily contrast medium. Lipiodol, and a high-molecular-weight anticancer agent known as SMANCS. SMANCS was dissolved in Lipiodol by sonication (SMANCS/Lipiodol, 1 mg of SMANCS in 1 ml of Lipiodol). SMANCS/Lipiodol, administered into the portal vein, remained for a long time in the portal vein and was eliminated gradually through the bile and urine. SMANCS/Lipiodol (0.4ml/kg) was injected into the mesenteric vein in rabbits, which were then inoculated with the highly malignant carcinoma VX-2. Rabbits injected with SMANCS/Lipiodol before inoculation had significantly fewer hepatic metastases than the control 12 days later (P less than 0.001). Survival was significantly longer (P less than 0.005; 36.0 +/- 7.7 days) with SMANCS/Lipiodol before inoculation than without treatment (23.5 +/- 3.0 days). Hepatic metastases might thus be prevented by portal administration of an appropriate oily anticancer agent.

Animals↗

Molecular cloning of a human apoC-III variant: Thr 74----Ala 74 mutation prevents O-glycosylation.

Apolipoprotein C-III (apoC-III) is a major protein of very low density lipoprotein (VLDL). The apoC-III polypeptide contains a carbohydrate chain containing galactosamine, galactose, and sialic acid attached in O-linkage to a threonine residue at position 74. We have cloned the apoC-III gene from a subject whose serum contained unusually high amounts of apoC-III lacking the carbohydrate moiety (C-III-0). DNA sequence analysis of the cloned gene revealed a single nucleotide substitution (A----G) that encodes an alanine at position 74 instead of the normal threonine. As a result of this amino acid replacement, the mutant apoC-III polypeptide is not glycosylated. The mutation in the apoC-III gene creates a novel AluI site that permits diagnosis of the change by Southern blotting of genomic DNA.

Alanine↗

[The nature of immunohistochemically defined astrocytic cells in rat gliomas].

The nature of astrocytic cells in rat gliomas induced by ethylnitrosourea (ENU) was studied by means of immunohistochemically demonstrating glial fibrillary acidic protein (GFAP), vimentin and beta-subunit of S 100 protein (S 100 beta) on paraffin sections. A special attention was paid to elucidating whether astrocytic cells would be neoplastic or not. The astrocytic cells in tumors were compared with astrocytes in normal rat brains and reactive astrocytes around a stab wound for their morphology, distribution and immunohistochemical characteristics. GFAP positive astrocytic cells in tumors were roughly divided into astrocytic cells and hypertrophic cells that showed morphologically similar appearance to fibrous astrocytes and hypertrophic reactive astrocytes around a stab wound respectively. A few multi-nucleated pleomorphic cells regarded as a kind of hypertrophic cells were also noted in gross tumors. GFAP positive cells were diffusely distributed in early neoplastic proliferations and microtumors, while in gross tumors they tended to be localized at the periphery. The GFAP positive cells were scattered among negative cells of tumors, forming no tumor mass. These findings suggest that the GFAP positive cells show no neoplastic growth, even though histopathologically they exhibit atypism or pleomorphism. The quantitative analysis of GFAP positive cells in tumors indicated more than 8% in most tumors in the white matter, whereas less than 8% in tumors in the gray matter and approximately 5% in gross tumors. The predominance of GFAP positive cells in the white matter was also observed in lesions induced by a stab wound.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗