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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 631 records · Page 35Linked to original sources
PubMed1991

Characterization of monoclonal anti-rabbit apolipoprotein E antibodies and chemical composition of lipoproteins separated by anti-apolipoprotein E immuno-affinity chromatography.

Six mouse monoclonal antibodies against rabbit apolipoprotein E (apo E) have been developed. Of these monoclonal antibodies, clone 5 revealed a high affinity for purified apo E, very low density lipoprotein (VLDL) and beta-VLDL. This monoclonal antibody was used to prepare an immunoaffinity column. Coupled to Sepharose 4B, this antibody allowed complete removal of lipoproteins containing apo E from plasma of New Zealand white (NZW) rabbits; 62, 46, 14, and 3% of VLDL-, IDL-, LDL-, and HDL-protein, respectively, were bound to the anti-apo E affinity column. The bound VLDL was significantly rich in free cholesterol (FC) and cholesteryl esters (CE) relative to the unbound VLDL, whereas bound IDL, LDL and HDL were significantly rich in FC only. All of the bound fractions were characterized by significantly increased ratios of FC/phospholipids (PL). These results indicate that the two lipoprotein populations with and without apo E have different lipid compositions. The relatively high content of cholesterol in lipoproteins containing apo E suggests a contribution of apo E to plasma cholesterol transport.

Animals↗
PubMed1991

[Changes of Cu, Zn-SOD and LPO in the regenerating liver after partial hepatectomy--effect of coenzyme Q10 administration].

We have investigated the effect of CoQ10 to lipid peroxide (LPO) and Cu, Zn-SOD in the regenerating liver in rats. Cu, Zn-SOD was investigated in biochemical activity, and immunohistochemical localization. In normal control liver, Cu, Zn-SOD was diffusely stained throughout the hepatic lobules, with predominance in the centrilobular area and with vicinity of thick portal vein. In early stage of regenerating liver. LPO was increased and Cu, Zu-SOD was decreased. Destruction of the membrane of hepatocyte was confirmed by electron microscopy in the early stage of regenerating liver, Cu, Zn-SOD might be speculated to leak out into extra cellular spaces. CoQ10 suppressed the mentioned phenomenon in regenerating liver.

Animals↗
PubMed1991

[Cross-resistance of HO-221 and various antitumor agents in sublines of mouse leukemia].

HO-221, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2- nitrobenzoyl) urea is a new benzoylphenylurea derivative. The compound exhibits significant antitumor effects against various animal tumors, and was especially effective against the solid tumors implanted subcutaneously. HO-221 inhibits DNA polymerase alpha activity strongly in vitro. In this study, we examined the cross-resistance of HO-221 to various antitumor agents using sublines of mouse leukemia. HO-221 showed antitumor effects in mice bearing L 1210 or P 388 leukemia resistant to 10 antitumor agents, DM (daunomycin), MMC (mitomycin C), CDDP (cisplatin), 5-FU (5-fluorouracil), Ara-C (cytosine arabinoside), MTX (methotrexate), CPA (cyclophosphamide), CQ (carboquone), ADM (adriamycin) and VCR (vincristine), respectively. These antitumor agents were also effective in P 388 leukemia resistant to HO-221 (P 388/HO-221). Furthermore, CDDP- and MMC-resistant sublines showed a collateral sensitivity to HO-221 in vivo. The grow the inhibitory effects were also noted in vitro in ADM-, CDDP- and MMC-resistant cells by HO-221. However, the in vitro experiments didn't show such collateral sensitivity on the resistant sublines. These results suggest that there is no cross-resistance between HO-221 and other known antitumor agents, and that HO-221 seemed to be worth for evaluating clinical usefulness.

Animals↗
PubMed1991

[Experimental study on the mechanism of the intrapulmonary kinetics of 123I-IMP in a balloon occluded bronchus in rabbits].

To investigate the mechanism of intrapulmonary kinetics of N-isopropyl-p-123I-iodoamphetamine (123I-IMP), we performed lung scanning with 123I-IMP in 13 rabbits in which a unilateral bronchus was occluded by a balloon catheter. In 9 rabbits, on the delayed distribution images, an abnormal accumulation of 123I-IMP was detected in the hypoperfusion area of the peripheral lung field of the occluded bronchus, which was detected on lung perfusion images with 99mTc-MAA. Comparison of early (a summation image during 20 seconds immediately after injection) and delayed (a summation image from 70 to 90 minutes after injection) distribution images confirmed that during this period, 123I-IMP accumulated in the area of reduced distribution of 123I-IMP. Moreover, at the site of abnormal accumulation, washout of 123I-IMP from the lung was delayed compared with that in the normal lung field. We find this experimental study is similar to the results in 63 clinical cases, which we have reported previously, and confirm that pulmonary arterial perfusion, especially hypoperfusion, influences the intrapulmonary kinetics of 123I-IMP.

Amphetamines↗
PubMed1991

[Combined effect of HO-221 with various antitumor agents against L 1210 leukemia].

Combined effect of N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea, HO-221, with various antitumor agents was studied using L 1210 leukemia in vivo and in vitro. Ten anticancer drugs were chosen from alkylating agents, antitumor antibiotics, antimetabolites and plant alkaloids each. The combined effect was assessed by comparing ILS (increase of life span) in the combined group with the sum of ILS of each single agent. Synergistic effect was considered to exist if ILS of the combination-treatment group exceeds the sum of those in 2 single-treatment groups. The two-drug combination of HO-221 with cyclophosphamide (CPA), adriamycin (ADM), mitomycin C (MMC), vindesine (VDS), vincristine (VCR) or etoposide showed remarkable synergistic effects with 60-days survivors. However, the combination chemotherapy with antimetabolites, 5-fluorouracil (5-FU) and methotrexate (MTX) showed competitive effects. Moreover, the synergistic cytocidal effect in vitro by the clonogenic assay was observed in combination of HO-221 with the same drug using in vivo test. The present results indicate that HO-221 seems to be a useful antitumor agent in combination chemotherapy.

Animals↗
PubMed1991

[Analysis of factors affecting hepatic dysfunction during group health checks for local inhabitants].

During health checks within the framework of the Geriatric Health Law, hepatic dysfunction was detected at a high incidence in inhabitants of K town. The factors affecting hepatic dysfunction in these cases were explored. The number of inhabitants who received health checks in 1989 in this town was 4,491 (78.5% of all inhabitants aged over 35 years). A diagnosis of hepatic dysfunction was made if GOT was equal to or higher than 41 IU/l or GPT was equal to or higher than 39 IU/l. On this basis, hepatic dysfunction was detected in 418 inhabitants (9.8%). The incidence of hepatic dysfunction was higher in males than in females. Inhabitants younger than 50 years had a higher incidence than those 50 years or older. The percentage of inhabitants with either a history of alcohol consumption or of receiving blood transfusion was significantly higher for inhabitants with hepatic dysfunction (29% and 10%, respectively) than for healthy inhabitants (10% and 3%, respectively). HBs antigen and anti HCV antibody positive rates for inhabitants with hepatic dysfunction were 3.3% and 36.1% respectively. These results suggest that the relatively high rate of hepatic dysfunction in this town is related to alcohol consumption, blood transfusion and hepatitis C virus (HCV) infection. Of these three factors, the influence of HCV infection seemed to be the most influential. The study additionally disclosed variations in the incidence of hepatic dysfunction among the different regions of the town probably related to regional differences in the anti-HCV antibody positive rate.

Adult↗
PubMed1991

Oxidation-labile subfraction of human plasma low density lipoprotein isolated by ion-exchange chromatography.

We isolated subfractions of human plasma low density lipoprotein (LDL) using ion-exchange chromatography. Plasma LDL from normolipidemic subjects were applied to a DEAE Sepharose 6B column. After elution of the bulk of LDL at 150 mM NaCl (the major fraction), the residual LDL was eluted at 500 mM NaCl and designated as the minor fraction. The minor fraction, only less than 1% of total LDL, tended to be somewhat similar in certain properties to oxidized LDL, e.g., an increased negative charge, higher protein/cholesterol ratio, and a higher flotation density than native LDL. These results were consistent with data reported by Avogaro et al. (1988. Arteriosclerosis. 8: 79-87). However, assays of 125I-labeled LDL binding activity for LDL receptors equal to that of the major fraction. Incorporation of [14C]oleate into cholesteryl ester [acyl-CoA:cholesterol acyltransferase (ACAT) activity] in mouse peritoneal macrophages incubated with the minor fraction was only slightly greater than that with the major fraction. Incubation of the minor fraction with 0.5 microM Cu2+ caused a remarkable stimulation of ACAT activity, while stimulation by the major fraction required incubation with 5 microM Cu2+, suggesting that the minor fraction was relatively labile to oxidation. The minor but definite presence of a plasma LDL subfraction more negative and susceptible to oxidation implicates the possibility of its association with atherogenesis.

Arteriosclerosis↗
PubMed1990

[CT evaluation of bone mineral density (BMD) of lumbar spine in patients after gastrectomy].

The late postoperative complications in patients after gastrectomy include anemia and metabolic bone disorders. We studied to determine whether gastric surgery is associated with metabolic bone disease. Vertebral BMD was measured in 55 patients after gastric resection by using DEQCT (dual energy quantitative CT). Forty patients were symptomatic, having bone or joint pain, history of bone fracture, or dental caries. The control group consisted of 161 patients without metabolic bone disorders. Forty percent of the patients with either the symptoms or history of bone fracture or dental caries, and 20% of the patients without the symptoms or the history showed decreased BMD. BMD was significantly lower in males in their 60s and in females in their 50s and 70s than BMD in age-matched control groups. When male subjects were grouped according to the years following the operation (1-5, 6-10, 11-15, 16-20 years), BMD was found to be decreased in 27%, 29%, 40% and 50% of the patients after surgery. Higher incidence of decreased BMD was found in the patients after total gastrectomy when compared with those after subtotal gastrectomy. Among the patients with subtotal gastrectomy, the incidence of decreased BMD was higher in patients with Billroth II anastomosis than in those with Billroth I anastomosis. In cases with compression fracture on thoracolumbar radiographs, BMD was significantly lower in comparison with cases with no fracture. It was difficult to differentiate between osteomalacia and osteoporosis only by the thoracolumbar radiographs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Morphological changes of taste buds and fungiform papillae following long-term neurectomy.

Long-term neurectomy of chorda tympani-lingual nerves results in a complete disappearance of taste buds from rabbit fungiform papillae. This supports the view that taste buds of mammalian fungiform papillae are neurally dependent. Furthermore, the covering epithelium of denervated fungiform papillae develops a characteristic keratinization pattern corresponding to that of filiform papillae.

Animals↗
PubMed1990

Effect of tumor necrosis factor/cachectin on the activity of the low density lipoprotein receptor on human skin fibroblasts.

We have investigated the effects of recombinant human tumor necrosis factor (TNF)/cachectin on the cellular binding of human low density lipoprotein (LDL) to human skin fibroblasts. When recombinant TNF was added to cultured cells, LDL binding doubled after 24 h of incubation. The effect of TNF was dose-dependent and its maximal effect was observed at concentrations of 1-10 ng/ml. TNF also stimulated the growth of human skin fibroblasts 1.6-fold. These results indicate that TNF increases LDL-receptor activity, which might be related to its stimulatory effect on cell growth.

Dose-Response Relationship, Drug↗
PubMed1990

Monocyte colony-stimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocyte-derived macrophages.

We have investigated effects of monocyte colony-stimulating factor (M-CSF) on the uptake of acetylated low density lipoproteins (acetyl-LDL) and the activity of cholesterol esterification in human monocyte-derived macrophage. The cells were cultured with M-CSF for 10 days and then incubated with acetyl-LDL for 24 h. M-CSF (128 ng/ml) enhanced the uptake and degradation of 10 micrograms/ml of 125I-acetyl LDL 7.5-fold (n = 6) and the effect of M-CSF was dose-dependent at the concentrations of 0.5-32 ng/ml. The binding experiments at 4 degrees C demonstrated that the number of acetyl-LDL receptor was increased by the addition of M-CSF. Supporting this, ligand blotting analysis revealed a significant increase in a receptor protein for acetyl-LDL (240 kDa). Binding of LDL was also enhanced by M-CSF but less significantly than that of acetyl-LDL. Cellular cholesterol esterification in the presence of 10 micrograms/ml acetyl-LDL was enhanced 24.1-fold (n = 13) by 128 ng/ml M-CSF. It was evident that M-CSF enhanced cholesterol esterification to a greater extent than the cellular uptake of acetyl-LDL (24.1- versus 7.5-fold). Cholesterol esterification was also enhanced by the addition of granulocyte-macrophage colony-stimulating factor and interleukin 1. We conclude that M-CSF enhances the uptake of both acetyl-LDL and LDL by increasing their receptor number, and further enhances the process of cholesterol esterification, resulting in a remarkable increase in cholesterol esterification in macrophages. These findings strongly suggest the significant involvement of cytokines such as M-CSF in cholesterol metabolism of macrophages.

Biological Transport↗
PubMed1990

Human monocyte colony-stimulating factor enhances the clearance of lipoproteins containing apolipoprotein B-100 via both low density lipoprotein receptor-dependent and -independent pathways in rabbits.

To investigate the effects of recombinant human monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism, we injected M-CSF intravenously into New Zealand White rabbits (n = 13) at a dose of 100 micrograms/day for 7 days. After the treatment, the plasma cholesterol levels fell by 33.2% from 61.4 +/- 25.9 to 41.0 +/- 10.2 mg/dl (mean +/- S.D.). We also injected a large dose of M-CSF (500 micrograms/day) for 6 days into Watanabe Heritable Hyperlipidemic rabbits, which are deficient in low density lipoprotein (LDL) receptors. Again, there was a significant reduction in plasma cholesterol levels by 36.2% from 730.5 +/- 176.4 to 466.0 +/- 104.9 mg/dl (n = 4). In the kinetic studies in New Zealand White rabbits with very low density lipoprotein, LDL, and methylated LDL, the removal rates of those lipoproteins were increased 1.9-, 1.7-, and 2.0-fold, respectively, after the treatment. Immunoblot analysis of LDL receptors in the treated rabbits showed no significant changes in LDL receptor proteins in livers but a great increase in spleens and bone marrows compared with the controls. Messenger RNA was also estimated by Northern blotting in both groups, and the results were compatible with those from the immunoblot. The data suggest that M-CSF stimulates the clearance of lipoproteins containing apolipoprotein B-100 via both LDL receptor-dependent and -independent pathways in target cells of M-CSF and reduces plasma cholesterol.

Animals↗
PubMed1990

Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer.

Adriamycin (ADR), an anthracycline anticancer drug, was bound to the poly(aspartic acid) chain of poly(ethylene glycol)-poly(aspartic acid) block copolymer by amide bond formation between an amino group of Adriamycin and the carboxyl groups of the poly(aspartic acid) chain. The polymeric drug thus obtained was observed to form a micelle structure possessing diameter of approximately 50 nm, with a narrow distribution, in phosphate-buffered saline and to show excellent water solubility despite a large amount of ADR introduction. Further, it was able to be stored in lyophilized form without losing its water solubility in the redissolving procedure. Increased stability of the bound Adriamycin molecules in phosphate-buffered saline and elimination of binding affinity for bovine serum albumin due to the micelle formation were further advantages of this polymeric drug. In vivo high anticancer activity of this micelle-forming polymeric drug against P 388 mouse leukemia was obtained with less body weight loss than that seen with free ADR, due to low toxicity as compared with free ADR.

Animals↗
PubMed1990

Apolipoprotein E and lipoprotein lipase secreted from human monocyte-derived macrophages modulate very low density lipoprotein uptake.

We investigated the roles of lipoprotein lipase and apolipoprotein E (apoE) secreted from human monocyte-derived macrophages in the uptake of very low density lipoproteins (VLDL). ApoCII-deficient VLDL were isolated from a patient with apoCII deficiency. The lipolytic conversion to higher density and the degradation of the apoCII-deficient VLDL by macrophages were very slight, whereas the addition of apoCII enhanced both their conversion and degradation. This suggests that the lipolysis and subsequent conversion of VLDL to lipoproteins of higher density are essential for the VLDL uptake by macrophages. VLDL incubated with macrophages obtained from subjects with E3/3 phenotype (E3/3-macrophages) showed a 17-fold greater affinity in inhibiting the binding of 2 micrograms/ml 125I-low density lipoprotein (LDL) to fibroblasts than native VLDL, whereas the incubation of VLDL with macrophages obtained from a subject with E2/2 phenotype (E2/2-macrophages) did not cause any increase in their affinity. Furthermore, 3 micrograms/ml 125I-VLDL obtained from a subject with E3/3 phenotype were degraded by E3/3-macrophages to a greater extent than by E2/2-macrophages (2-fold), indicating that VLDL uptake is influenced by the phenotype of apoE secreted by macrophages. From these results, we conclude that both lipolysis by lipoprotein lipase and incorporation of apoE secreted from macrophages alter the affinity of VLDL for the LDL receptors on the cells, resulting in facilitation of their receptor-mediated endocytosis.

Apolipoprotein C-II↗
PubMed1990

Vesicles with lactate dehydrogenase and without alkaline phosphatase present in the resting zone of epiphyseal cartilage.

Matrix vesicles are membrane-invested vesicles that initiate mineralization in the extracellular matrix of calcifying tissues. The epiphyseal cartilages of young-rat rib bones were divided into the growth zone and the resting zone, followed by the isolation of matrix vesicles after collagenase treatment. Matrix vesicles with both alkaline phosphatase and lactate dehydrogenase were detected in the growth cartilage found in the epiphyseal growth plates of young rabbits [Hosokawa, Uchida, Fujiwara & Noguchi (1988) J. Biol. Chem. 263, 10045-10047], but were not detected in the resting zone. By contrast, and surprisingly, lactate dehydrogenase-containing vesicles without alkaline phosphatase were found in the resting zone, but not in the growth zone. In both the growth and resting zones, isoenzyme patterns of lactate dehydrogenase in the two different vesicles were identical with those of cytosolic lactate dehydrogenase of chondrocytes, suggesting the presence of a mechanism for specific uptake of cytosolic lactate dehydrogenase. The same results as for young-rat rib bones were obtained with the resting and growth cartilages of young-dog and monkey rib bones.

Alkaline Phosphatase↗
PubMed1990

Mechanism of tumor cell killing by HO-221, a novel antitumor compound.

The mechanism of tumor cell killing by HO-221, a novel benzoylphenylurea derivative that shows broad-spectrum antitumor activities, was studied. HO-221 strongly inhibited the activity of mammalian DNA polymerase alpha but not that of DNA polymerases beta or gamma. The inhibition was equivalent to that induced by aphidicolin and ara-CTP, which were selective inhibitors of the enzyme. Furthermore, the inhibition by HO-221 of DNA polymerase alpha was found to be non-competitive with respect to dCTP as a substrate, unlike that induced by aphidicolin and ara-CTP. The inhibition was reduced the addition of an excess of DNA polymerase alpha but not by excess amounts of activated DNA as a template primer. These results suggest that HO-221 inhibits the activity of DNA polymerase alpha by direct interaction with the enzyme in contrast to the impairment of template activity through intercalation into DNA induced by anthracycline compounds. On the other hand, HO-221 showed almost no effect on RNA polymerase activity, the reverse transcriptase activity of avian myeloblastosis virus or protein synthesis in a cell-free system. The flow-cytometry analysis revealed that HO-221 accumulated HL-60 cells in G1-S phases at a low concentration but increased the number of cells in the G1 phase at a higher concentration, stopping cell-cycle progression. The results suggest a correlation between cell-cycle progression and inhibition by HO-221 of DNA polymerase alpha, which plays a role in DNA replication during the S phase in living cells.

Animals↗