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T Mayumi

Publications and source records attributed to T Mayumi.

At least 127 records · Page 7Linked to original sources
PubMed1996

Binding of Cd to metallothionein in the placenta of Cd-treated mouse.

The toxicological significance of the placental metallothionein (MT) was studied from the viewpoint of cadmium (Cd) intoxication. The Cd concentration was higher in the placenta than the kidneys until 8 hr after a single injection of 109CdCl2, but was very low after administration of 109Cd-MT. Compared with lower doses, fetal Cd began to increase at the dose of 2 mg/kg. Alkaline phosphatase activity in the placenta was significantly decreased, and dead fetuses appeared at this dose. The MT concentration was not increased by the Cd injection but the ratio of Cd/Zn in MT increased proportionally to the dose up to 2 mg/kg. MT was detected in the placenta during all stages of pregnancy, and its concentration was higher in the earlier stage. The metal bound to MT was mainly Zn, and very little Cu was bound. In the mice that became pregnant after 109Cd accumulation, redistribution of 109Cd was not observed. MT-I and -II in the placenta were identified by column chromatography and immunoblotting methods. These findings suggest that the placental MT might play a protective role against Cd toxicity by trapping of the metal.

Alkaline Phosphatase↗
PubMed1996

Molecular design of hybrid tumor necrosis factor-alpha III: polyethylene glycol-modified tumor necrosis factor-alpha has markedly enhanced antitumor potency due to longer plasma half-life and higher tumor accumulation.

We have reported that chemical modification of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG) markedly increases its antitumor potency without any adverse side effects. MPEG-TNF-alpha, especially, in which 56% of the lysine amino groups of TNF-alpha are coupled with PEG, exhibits 100-fold more antitumor activity in vivo than native TNF-alpha in the Meth-A murine sarcoma model. In this study, we investigated the pharmacokinetics of PEG-modified TNF-alpha with various molecular sizes to clarify the mechanisms of the enhanced antitumor potency of MPEG-TNF-alpha. The plasma half-lives of modified TNF-alpha increased with increasing molecular size. The decreased plasma clearance of modified TNF-alpha was partially caused by the shielding effect of the proteolytic sites in TNF-alpha by the attached PEG and the decreased transport from blood to various tissues. Almost all native TNF-alpha was uniformly distributed to the kidney and reticuloendothelial system within 1 hr of an intravenous administration, and rapidly disappeared from these tissues at 3 hr. However, very little native TNF-alpha was transported into the tumor. The absolute distributed amount and distribution profile of modified TNF-alpha to tissues other than the tumor were the same as those of native TNF-alpha, whereas the plasma levels of the modified TNF-alpha were higher than plasma levels of the native TNF-alpha. The tumor distribution of modified TNF-alpha was markedly enhanced compared with native TNF-alpha and gradually increased over time. About 9-fold more MPEG-TNF-alpha was distributed to the tumor than native TNF-alpha. Thus, we found that the marked increase in the antitumor potency of PEG-modified TNF-alpha resulted from the enhanced blood residency and tumor accumulation. The antitumor effect of MPEG-TNF-alpha against sarcoma-180 other than Meth-A fibrosarcoma was also about 100 times greater than that of native TNF-alpha when systemically administered. The optimal PEGylation of TNF-alpha facilitated its antitumor potency and MPEG-TNF-alpha may be useful systemic antitumor therapeutic drug.

Animals↗
PubMed1996

Zonal heterogeneity of hepatic injury following shock/resuscitation: relationship of xanthine oxidase activity to localization of neutrophil accumulation and central lobular necrosis.

Post-ischemic hepatic injury is characterized by zonal heterogeneity of injury (central lobular necrosis), sinusoidal neutrophil accumulation, and injury generated by reactive oxygen metabolites. We evaluated the role of the heterogeneous distribution of hepatic xanthine oxidase in the generation of neutrophil accumulation and consequent hepatocellular injury in rats subjected to shock [controlled hemorrhagic hypotension (mean arterial pressure = 37.5 + or - 2.5 mmHg for 120 min)], with or without subsequent resuscitation and hemodynamic stabilization, compared with sham-operated rats. Shock/resuscitation produced striking neutrophil accumulation (assayed by esterase histochemistry) in the pericentral sinusoids, associated with centrolobular necrosis. This paralleled the pericentral distribution of xanthine oxidase (determined by histochemical assay of frozen sections) and its release from the liver into the circulation at resuscitation. Pretreatment with allopurinol inhibited hepatic xanthine oxidase activity, neutrophil accumulation, and pericentral hepatocyte necrosis in shock/resuscitation in rats. These findings suggest that reactive oxygen metabolites generated by heterogeneously distributed xanthine oxidase may contribute to the heterogeneity of hepatocellular injury in "ischemic hepatitis."

Animals↗
PubMed1995

Tumor-conditioned medium increases macromolecular permeability of endothelial cell monolayer.

The permeation of macromolecular FITC-labeled dextran (molecular weight 70,000) through bovine aortic endothelial cells (BAEC) monolayer, which were cultured for 5 days with conditioned medium prepared from mouse melanoma B16, was increased. However, when BAEC, which were cultured with normal medium until confluent, were treated with B16 conditioned medium (B16-CM) for 30 min, the permeability did not increase. The B16-CM also increased the permeability of the endothelial monolayers of bovine veins and the human umbilical vein, but did not increase that of the epithelial monolayer. The B16-CM did not alter the distribution or content of F-actin on the BAEC. BAEC cultured in the presence of B16-CM for 5 days were detached from the dish, and then seeded into a chamber at one-fifth of confluent cell density. After 5 days of culture in normal medium, the BAEC were grown to confluence and their permeability was increased. These findings suggest that B16-CM increased the endothelial permeability irreversibly without the decrease of F-actin, and that soluble factor(s) which were secreted from the tumor cells participate in the construction of the hyperpermeable structure of tumor vessels in vivo.

Actins↗
PubMed1995

Ascorbic acid stimulates barrier function of cultured endothelial cell monolayer.

The macromolecular permeability of cultured bovine aortic, bovine venous, and human umbilical vein endothelial cell monolayers was decreased significantly in culture medium containing L-ascorbic acid (Asc Acid; 0.01-0.1 mM) and L-ascorbic acid 2-phosphate (Asc 2-P). Dithiothreitol, which shows reducing activity equivalent to that of Asc Acid, did not affect endothelial permeability. Asc Acid induced a sixfold increase in collagen synthesis by the endothelial cells. The coexistence of L-azetidine 2-carboxylic acid, an inhibitor of collagen synthesis, attenuated the effect of Asc 2-P in a dose-dependent manner. Another collagen synthesis inhibitor, ethyl-3,4-dihydroxybenzoate, also inhibited collagen synthesis and increased endothelial permeability. The decrease in permeability of the endothelial monolayer was dependent on a reduction of the permeability coefficient of the endothelial monolayer. These findings indicate that endothelial barrier function is stimulated by Asc Acid via an increase in collagen synthesis.

Animals↗
PubMed1995

Molecular design of hybrid tumour necrosis factor alpha with polyethylene glycol increases its anti-tumour potency.

This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use.

Animals↗
PubMed1995

Isolation and properties of tumor-derived endothelial cells from rat KMT-17 fibrosarcoma.

Rat KMT-17 fibrosarcoma-derived endothelial cells were isolated by Percoll gradient centrifugation with an attaching-speed separation technique, and their properties in culture were examined. The primary cultured tumor-derived endothelial cells (TEC) showed angiotensin-converting enzyme activity, positivity for Factor VIII-related antigen staining, and typical capillary-like formation on Matrigel. The primary cultured TEC monolayer showed greater permeability than normal tissue-derived endothelial cell (aorta, vena cava and epididymal fat capillary) monolayers on FITC-dextran diffusion (molecular weight 70,000). Leukocyte adhesion to TEC was reduced compared to that to fat-derived capillary endothelial cells. These characteristics resembled those of tumor vascular endothelium, and were observed both in the primary and first-passage cell cultures, but not in the fourth-passage cell cultures. Our findings indicate that primary or subcultured TEC are applicable for studies of the physiological characteristics of tumor endothelial cells.

Animals↗
PubMed1995

A quantative in vivo method of analyzing human tumor-induced angiogenesis in mice using agarose microencapsulation and hemoglobin enzyme-linked immunosorbent assay.

This study was conducted to develop a quantitative assay system for use in the in vivo evaluation in mice of angiogenesis induced by human tumor cells. The human epidermoid carcinoma cells, A431 cells, were cultured on microcarriers. Microcarrier-attached A431 cells (A431-MC) were microencapsulated with agarose hydrogel to isolate them from the immune system of the C57BL/6 mice after subcutaneous dorsal midline implantation. The agarose hydrogel-microencapsulated A431 cells (Aga-A431 cells; diameter=300 micron) survived for at least 10 days in vitro, and the proliferation profile of the Aga-A431 cells was indistinguishable from that of non-microencapsulated A431 cells. The Aga-A431 cells were subcutaneously injected into mice with an 18-gauge needle. Ten days later, few vessels had formed at the site implanted with cell-free agarose beads, whereas notable angiogenesis was observed at the site implanted with Aga-A431 cells. The degree of angiogenesis was evaluated by measurement of the hemoglobin content in the implanted site using a mouse hemoglobin (mHb) enzyme-linked immunosorbent assay (ELISA) system. This mHb-ELISA system has the advantages of great simplicity and reproducibility. The measured mHb-content of new blood vessels at the site implanted with agarose beads was in good agreement with the amount of angiogenesis observed under a stereoscopic microscope. This assay system enabled us to evaluate the angiogenesis induced by xenogeneic cells, such as human tumor cells. Thus, our novel method may be useful for the study of the angiogenic potential of various human tumor cells and in research on the anti-angiogenic properties of various agents.

Animals↗
PubMed1995

Amino acids and peptides. XXV. Preparation of fibronectin-related peptide poly(ethylene glycol) hybrids and their inhibitory effect on experimental metastasis.

Hybrids of fibronectin-related peptides [Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGDS)] and poly(ethylene glycol) (PEG) were prepared and their inhibitory effects on experimental metastasis in mice were examined. The inhibitory effect of RGD was markedly potentiated by hybrid formation with poly(ethylene glycol) #6000. As to inhibitory effect, RGD was more potent than RGDS and RGD PEG hybrids were superior to RGDS PEG hybrids. Hybrid formation with PEG #6000 was more effective than that with PEG #4000.

Amino Acid Sequence↗
PubMed1995

[A case of hemophagocytic syndrome manifesting adult Still's disease and acute hepatitis].

We report a 20 year-old woman with hemophagocytic syndrome. In February 1993, she developed high fever, arthralgia, salmon-like pink eruption, leukocytosis and splenomegaly. She was diagnosed as adult Still's disease and successfully treated with intravenous immunoglobulin and oral prednisolone. In September 1993, she was re-admitted to our hospital complaining of general fatigue and low grade fever and treated with oral prednisolone at a daily dose of 15 mg. On October 2, 1993, she suddenly developed high fever and salmon-like pink eruption on her leg followed by the marked increase of serum transaminase and LDH levels (GOT 3,270 IU/l, GPT 1,880 IU/l, LDH 5,480 IU/l) on October 7. Since hepatic failure progressed, we started methylprednisolone pulse therapy and plasmapheresis. However, because of the progression of pancytopenia caused by hemophagocytosis, the treatment with VP-16 was initiated. However, she died of DIC on November 2, 1993. Autopsy revealed submassive necrosis of the hepatocytes with moderate infiltration of histiocytes. She was retrospectively diagnosed as hemophagocytic syndrome whose manifestations are very similar to those in adult Still's disease and acute viral hepatitis.

Acute Disease↗
PubMed1995

Synthetic cell-adhesive laminin peptide YIGSR conjugated with polyethylene glycol has improved antimetastatic activity due to a longer half-life in blood.

This study was conducted to determine the mechanisms for the enhanced inhibitory effect of cell-adhesive peptides conjugated to polyethylene glycol (PEG) on tumor metastasis. Tyr-Ile-Gly-Ser-Arg (YIGSR), a laminin-derived peptide, conjugated with amino-PEG (YIGSR-aPEG) inhibited lung metastasis of B16-BL6 melanoma cells more effectively than unconjugated YIGSR peptide. [125I]-YIGSR-aPEG and native [125I]-YIGSR showed similar biphasic elimination and profiles after intravenous injection into C57BL/6 mice. Both [125I]-YIGSR and [125I]-YIGSR-aPEG expressed similar plasma half-lives and organ distributions. The radioactivity of both compounds was transported rapidly from the blood to the kidneys, and immediately excreted into the urine. [125I]-YIGSR was almost completely degraded in the urine, but [125I]-YIGSR-aPEG was not. In an in vitro stability assay, [125I]-YIGSR was degraded immediately upon incubation with mouse serum, whereas [125I]-YIGSR-aPEG was not degraded after 180 min incubation in mouse serum. These findings indicate that the enhanced inhibitory effect of YIGSR-aPEG on lung metastasis might be due to its increased stability in the blood.

Animals↗
PubMed1994

Glial extracellular matrix modulates gamma-glutamyl transpeptidase activity in cultured bovine brain capillary and bovine aortic endothelial cells.

Glial extracellular matrix (ECM) elevated gamma-glutamyl transpeptidase (gamma-GTP) activity in cultured bovine brain capillary and aortic endothelial cells (BBCEC, BAEC). In particular, the ECM of glial cells cultured with the conditioned medium of BAEC (BAEC CM) dramatically elevated gamma-GTP activity in BBCEC and BAEC. The ECM of glial cells cultured with BBCEC CM also had a marked effect. The ECM of 3T3 cells cultured with BAEC CM, and the ECM of glial cells cultured with 3T3 CM had no effect. Glial CM had no effect on gamma-GTP activity in BBCEC and BAEC. These findings indicate that gamma-GTP activity in endothelial cells (EC) is modulated by glial ECM, and that the factor of ECM that affects gamma-GTP activity in EC arises from the interaction between glial cells and EC.

Animals↗
PubMed1994

Flow cytometric analysis of mouse sperm using monoclonal anti-sperm antibody A-1.

We have previously prepared an anti-mouse sperm monoclonal antibody (A-1) which inhibited sperm penetration into the egg zona pellucida. By indirect immunofluorescence (IIF), the A-1 antibody was shown to recognize an antigen localized in the acrosomal area of sperm. This antibody bound negligibly to fresh sperm, while binding to methanol-fixed sperm was almost complete. After methanol fixation, no sperm that penetrated into the zona were immunoreactive for this antibody. In the present study we examined the localization and fate of A-1 antigen during the acrosome reaction by IIF and flow cytometry (FCM). Cauda epididymal sperm were treated with either calcium ionophore A23187 or zona solution, immunostained indirectly, and subjected to FCM. Treatment with A23187 reduced the percentage of immunoreactive sperm to 59% from the 80% obtained in the untreated sperm. The treatment also reduced the average fluorescence intensity per fluorescence-positive spermatocyte to 65 channels, while this intensity was 89 channels in the untreated sperm. A similar result was obtained from treatment with zona solution. The proportion of sperm that was immunoreactive with A-1 antibody was reduced to 55% by incubation in zona-containing media from the 80% obtained in zona-free media. On the other hand, neither A23187 nor the zona solution affected the immunoreactivity or the fluorescence intensity of caput epididymal sperm, while the A-1 antigen was present in both the immature sperm from the caput epididymis of adult mice and in the mature sperm from the cauda epididymis of the same mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗
PubMed1994

Imaging study on the mode of development and changes in avascular necrosis of the femoral head in systemic lupus erythematosus: long-term observations.

To find out when and how avascular necrosis of the femoral head (ANFH) develops in patients with SLE who are receiving corticosteroids, we carried out a 3-yr prospective study using imaging methods. Twenty-three patients with SLE who were free of hip pain and radiographically negative were enrolled in the study. Initially, abnormal findings characteristic of ANFH were detected in eight (35%) and six (26%) patients on MRI and radionuclide uptake bone scanning, respectively. During a 3-yr observation period abnormalities on MRI, bone scanning and radiography were found in four, five and four patients, respectively and three patients developed hip pain. Analyses of imaging changes demonstrated that only a small proportion of patients (2/8, 25%) who initially showed abnormal MRI progressed to be radiographically positive for ANFH over the 3 years. High doses of corticosteroids over the 3-yr period were to be responsible for the emergence of change in MRI abnormalities. It is also suggested that abnormal MRI findings tend to develop either within a relatively short interval after the start of corticosteroid treatment or are associated with the exacerbation of SLE.

Adolescent↗
PubMed1994

Noninvasive, continuous blood pressure measurement by arterial tonometry during anesthesia in children.

BACKGROUND: The authors' previous study of arterial tonometry in children demonstrated poor agreement of tonometric blood pressure (TBP) measurements with intraarterial blood pressure (IBP) measurements. The aim of the current study is to evaluate the feasibility of TBP measurements in children aged 1-6 yr using a newly designed pediatric sensor housing, by comparing TBP values with values obtained by IBP measurements. METHODS: Thirty-four children (aged 1-6 yr, ASA physical status 1-2) were studied undergoing elective abdominal or urologic surgery under general anesthesia. A 22- or 24-G cannula was inserted into the right radial artery. A TBP sensor housing was positioned over the left radial artery. TBP and IBP were continuously monitored and data were periodically sampled during and after intubation, during surgery, and during the recovery period. RESULTS: TBP waveforms were similar to those of IBP. Limits of agreement (bias +/- 2 SD) were 12 and -13.3 mmHg for systolic, 11.6 and -10.4 mmHg for mean, and 13.2 and -10.8 mmHg for diastolic pressures for 3,400 paired points. Measurements could not be made in ten children because of insufficient pulse contour. CONCLUSIONS: When pulse contour is sufficient for analysis, TBP monitoring provides an apparently safe and accurate method for the continuous measurement of arterial blood pressure during anesthesia in children aged 1-6 yr.

Anesthesia↗
PubMed1994

Antimetastatic effects of synthetic peptides containing the core sequence of the type III connecting segment domain (IIICS) of fibronectin.

The antimetastatic activities of synthetic peptides corresponding to fragments of the adhesion-related molecules, such as fibronectin and laminin, were examined. We prepared three peptides derived from the type III connecting segment domain (IIICS) of fibronectin: Glu-Ile-Leu-Asp-Val (EILDV), Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (EILDVPST), Arg-Glu-Asp-Val (REDV), and a laminin-related peptide, Tyr-Ile-Gly-Ser-Arg (YIGSR). Each peptide inhibited the experimental tumor metastasis of B16-BL6 melanoma, while EILDV had the strongest effect. The peptides conjugated with poly(ethylene glycol) (PEG) were more effective than the unmodified peptides in molar ratio terms. A mixture composed of PEG hybrids with EILDV, REDV and YIGSR significantly inhibited tumor metastasis.

Amino Acid Sequence↗