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Biomedical subjects

S Toyama

Publications and source records attributed to S Toyama.

At least 37 records · Page 2Linked to original sources
PubMed1995

Comparison of the chase effects of avidin, streptavidin, neutravidin, and avidin-ferritin on a radiolabeled biotinylated anti-tumor monoclonal antibody.

Injection of avidin can decrease the background radioactivity due to a radiolabeled biotinylated monoclonal antibody. We compared the chase effects of avidin, streptavidin, neutravidin, and avidin-conjugated ferritin on a radiolabeled antitumor monoclonal antibody in tumor-bearing nude mice. A radioiodine-labeled biotinylated monoclonal antibody (OST7) was administered to athymic mice bearing osteogenic sarcomas. After 24 h, an avidin, streptavidin, neutravidin or avidin-conjugated ferritin chaser was intravenously injected into the mice. At 2 h after the chase, the biodistribution of the radiolabeled monoclonal antibody was determined. Clearance from the blood was dose-dependently accelerated by avidin and its effect was 10-fold stronger than that of neutravidin or avidin-ferritin. Streptavidin did not promote clearance of the biotinylated antibody. Avidin was the most effective chasing agent for improving the biodistribution of the radiolabeled biotinylated monoclonal antibody among the four avidin derivatives tested.

Animals↗
PubMed1995

Disposition of polaprezinc (zinc L-carnosine complex) in rat gastrointestinal tract and effect of cimetidine on its adhesion to gastric tissues.

The disposition of polaprezinc in the rat gastrointestinal tract was studied by a double tracer method using [14C]- and [65Zn]polaprezinc. At 0.5 h after oral administration of [14C]-,[65Zn]polaprezinc to rats, the 14C-radioactivity in the gastric contents was comparable with the 65Zn-radioactivity. However, a significant difference was observed in the time course of changes in gastric contents between 14C- and 65Zn-radioactivity over 1 h after administration, indicating that polaprezinc existed in complex form at 0.5 h after administration and was dissociated to L-carnosine and zinc in the gastrointestinal tract as a function of time. The adhesion of zinc to stomach mucosa after oral administration of polaprezinc to rats was significantly increased by treatment with cimetidine. These results suggest that the adhesion of zinc to gastric tissues is increased by inhibiting the dissociation of polaprezinc, and that H2-receptor antagonists, such as cimetidine, may increase anti-ulcer effects of polaprezinc.

Administration, Oral↗
PubMed1995

Residence time of polaprezinc (zinc L-carnosine complex) in the rat stomach and adhesiveness to ulcerous sites.

Polaprezinc, an insoluble zinc complex of L-carnosine, exhibits anti-ulcer effects by acting directly on mucosal lesions. The disposition of polaprezinc in the stomach was studied to clarify the usefulness of its structure as an insoluble complex. The time courses of 14C-radioactivity in the gastric contents and gastric tissues were parallel to those of 65Zn after oral administration of a mixture of 14C-polaprezinc and 65Zn-polaprezinc (14C-, 65Zn-polaprezinc) to rats. The gastric contents of 14C-polaprezinc and 65Zn-polaprezinc were greater than those of 14C-L-carnosine and 65ZnSO4. Mean residence times (MRT) of 14C-polaprezinc and 65Zn-polaprezinc in the stomach were almost the same (ca. 2 hr), and they were double those of 14C-L-carnosine and 65ZnSO4. In gastric tissues, the area under the concentration curves (AUC0-8 hr) of 14C-polaprezinc and 65Zn-polaprezinc were 1.7 times greater than those of 14C-L-carnosine and 65ZnSO4, respectively. After administration of 14C-, 65Zn-polaprezinc to rats with acetic acid-induced ulcers, 14C and 65Zn-radioactivities in the ulcerous sites were very similar and greater than those of 14C-, 65Zn-polaprezinc dissolved in acid. In conclusion, polaprezinc is retained in the stomach longer and adheres to the ulcerous sites more than zinc or L-carnosine. The characteristics of this compound may arise from its insolubility and contribute to its strong pharmacological action.

Animals↗
PubMed1994

Characterization of the antihemorrhagic factors of mongoose (Herpestes edwardsii).

Three antihemorrhagic factors (AHF1, AHF2 and AHF3) isolated from the serum of mongoose (Herpestes edwardsii) are glycoproteins of monomer structure with the same mol. wt (about 65,000), which contain 4.2%, 13.6% and 6.0% carbohydrates as glucose, respectively. All are composed of about 600 amino acids of similar composition. The 32 amino terminal amino acid sequences of three antihemorrhagic factors were determined, and sequence homologies were examined. AHF1 and AHF2 were of the same amino acid sequence, and showed high homologies to AHF3, oprin (opossum proteinase inhibitor) and human alpha 1B-glycoprotein; 68.7%, 42.3% and 50.0% identity, respectively. AHF1 completely inhibited the hemorrhagic activity of HR2b, the hemorrhagic factor of habu snake, at the concentration of five-fold molar excess, although incomplete inhibition (50%) of proteinase activity of the hemorrhagic factor was observed even at the concentration of 20-fold molar excess of antihemorrhagic factor. Incubation of HR2b with AHF1, and analysis of the reaction products by chromatography on TSK gel G-3000SW and on the ultracentrifuge did not show formation of an inactive enzyme inhibitor complex. However, the complex formation between AHF1 and HR2b was observed by a BIAcore analysis and TSK gel SP-5PW column chromatography. No alteration in the primary or the secondary structure of both factors was demonstrated by SDS-PAGE and circular dichroism spectrum at the far-UV wavelength before and after incubation of both factors, respectively.

Amino Acid Sequence↗
PubMed1994

Interference with the endosomal acidification by a monoclonal antibody directed toward the 116 (100)-kD subunit of the vacuolar type proton pump.

A monoclonal antibody (OSW2) was prepared by using human osteosarcoma cells. OSW2 was found to be directed toward the 116 (also called 100)- kD protein that uniquely associates to the vacuolar-type proton pump. The antibody specifically localized acidic membrane compartments that could be visualized with acridine orange in many types of human cells. It also reacted with the surface and was internalized along the endosomal pathway. Monitoring the endosome pH by using FITC-dextran and acridine orange suggested that the antibody interfered with low pH. Cell-free experiments indicated that the ATP-dependent acidification was inhibited in endosomes associated with OSW2. In contrast, the antibody gave little effect on the ATPase activity of the solubilized H+ pump. The internalization of OSW2 reduced infectivity of certain enveloped viruses (influenza, SFV, VSV) by 50 to 80%. Inhibition of viral fusion was directly demonstrated by monitoring the fate of octadecylrhodamine-labeled influenza virus fluorescence. These results indicate that the 116 (100)-kD protein is necessary for the control of pH. The antibody represents a novel probe for understanding the role of the endosomal compartments in cellular physiology.

Adenosine Triphosphate↗
PubMed1994

Absorption mechanism of polaprezinc (zinc L-carnosine complex) by an everted sac method.

1. The absorption mechanism of polaprezinc (zinc-carnosine chelate compound) was studied in rat by an everted gut sac method. The rates of transport and accumulation of 14C-L-carnosine were proportional to the mucosal concentration of L-carnosine, whereas the rates of transport and accumulation of 65ZnCl2 had become saturated. The Michaelis-Menten constant (Km) = 4.41 mM and maximal rate (Vmax) = 71.83 nmol/min/g for zinc transport and, similarly, Km = 6.21 mM and Vmax = 92.51 mumol/30 min/g for accumulation. 2. The addition of ouabain, 2,4-dinitrophenol (2,4-DNP) and low temperatures reduced the rate of zinc uptake, indicating that zinc transport was considered to be a carrier-mediated process based on Na+,K(+)-ATPase-dependent mechanisms. 3. The concentration of zinc in the gut of the non-fasted rat was greater than that of the fasted rat, suggesting different rates of transport and accumulation. It is suggested that zinc intestinal uptake in rat is regulated by zinc content in the gut. 4. A pharmacokinetic model for transport and accumulation of zinc saturation from the lumen side to the gut was designed, and the calculated values obtained by simultaneous multiline fitting of transport and accumulation of zinc data were in good agreement with the observed values.

Animals↗
PubMed1994

Improved clearance of radiolabeled biotinylated monoclonal antibody following the infusion of avidin as a "chase" without decreased accumulation in the target tumor.

UNLABELLED: The techniques of radioimmunoimaging and radioimmunotherapy suffer from prolonged high background radioactivity because intravenously injected antibodies remain in the circulation and in the organs far longer than necessary for effective binding to the target. To decrease background and increase radionuclide excretion without decreasing the dose of radioactivity delivered to the target tumor, we used radiolabeled biotinylated antibodies followed by a "chase" avidin injection. METHODS: A mouse monoclonal antibody, OST7 (IgG1), which reacts with human osteosarcoma, was biotinylated and labeled with 125I, 131I or 99mTc. Radiolabeled biotinylated OST7 (10 micrograms) was administered intravenously into nude mice bearing human osteosarcomas and 30 micrograms of avidin was injected intravenously 6 or 24 hr later. RESULTS: Following avidin injection in mice pretreated with radiolabeled biotinylated antibodies, radioactivity was promptly cleared from the blood and deposited in the liver and spleen, after which radioiodine was rapidly detached from the antibody and excreted in the urine. The tumor-to-blood ratios at 6 and 24 hr after the injection of 125I-labeled biotinylated OST7 increased compared with the values before the avidin chase without any loss of tumor radioactivity. Furthermore, the tumor-to-background radioactivity ratio was improved and better images were obtained more rapidly after the injection of radiolabeled biotinylated antibodies than with conventional immunoscintigraphy. CONCLUSIONS: This method may find application in clinical radioimmunoimaging, especially using short half-life radionuclides such as 99mTc and 123I.

Animals↗
PubMed1993

In vivo instability of reduction-mediated 99mTc-labeled monoclonal antibody.

A murine monoclonal antibody that reacts with human osteogenic sarcoma (OST7) was reduced and directly labeled with 99mTc without any loss of immunoreactivity. No fragmentation of the antibody was detected by high performance liquid chromatography after the labeling. However, SDS-PAGE analysis of the labeled antibody demonstrated the presence of low molecular weight species. Although more than 95% of the radioactivity remained bound at the antibody after incubation with human serum for 24 h, 99mTc-labeled OST7 was cleared faster from the circulation than 125I-labeled OST7 or 111In-labeled OST7 in mice. Urinary and fecal excretion of 99mTc were higher than those of 125I. When the 125I-labeled antibody was dual-labeled with 99mTc, the blood clearance of 99mTc was faster than that of 125I, suggesting release of 99mTc from the antibody in vivo. 99mTc-labeled OST7, however, gave a higher tumor-to-blood ratio than 125I- or 111In-labeled OST7 in mice bearing human osteogenic sarcoma. The 99mTc-labeled antibody prepared by the direct method was unstable in vivo, but retained a good tumor targeting ability.

Animals↗
PubMed1992

Direct proof that the primary site of action of cytochalasin on cell motility processes is actin.

We have previously described the isolation of a mutant KB cell (Cyt 1 mutant) resistant to the cytotoxic effect of cytochalasin B (CB). The Cyt 1 mutant carries an altered form of beta-actin (beta'-actin) and lacks normal beta-actin (Toyama, S., and S. Toyama. 1984. Cell. 37:609-614). Increased resistance of the Cyt 1 mutant to CB in vivo is reflected in altered properties of beta'-actin in vitro (Toyama, S., and S. Toyama. 1988. J. Cell Biol. 107:1499-1504). Here, we show that the mutation in beta-actin is solely responsible for the cytochalasin-resistant phenotype of the Cyt mutant. We have isolated a cDNA clone encoding beta'-actin from Cyt 1 cells. Sequence analysis reveals two mutations in the coding region that substitute two amino acid residues (Val139----Met and Ala295----Asp). Expression of the beta'-actin cDNA confers cytochalasin resistance upon transformed cytochalasin-sensitive KB cells. Levels of resistance to CB in the transformed cell clones correlate well with amounts of beta'-actin polypeptide. Both of the two mutations in beta'-actin are necessary for the high level expression of cytochalasin resistance. Overall, we conclude that the primary site of action of cytochalasin on cell motility processes in vivo is actin.

Actin Cytoskeleton↗
PubMed1992

[The gastric mucosal adhesiveness of Z-103 in rats with chronic ulcer].

The gastric mucosal adhesiveness of Z-103 in rats with acetic acid ulcer was studied macroscopically, histologically, and biochemically. From macroscopical observations, when Z-103 was orally administered to an acetic acid ulcer model, there was adhesion of Zn to the normal mucosa as well as the ulcerous site under both the fasting condition and after feeding. It was also proven that the strength and duration of adhesiveness were increased dose-dependently under fasting conditions. In addition, histological localization of Zn was noted from the covering epithelial cell layer to the gastric lamina propria mucosae in the normal tissue and in the most superficial ulcerous layer and the granulous layer of the ulcerous site. Measurement of the gastric tissue Zn content after oral administration of 100 mg/kg of Zn showed that the Zn content was significantly increased for 6 hr at the normal site and for 24 hr at the ulcerous site. On the other hand, although ZnSO4 and ZnSO4+carnosine combination macroscopically produced generally the same level of adhesiveness as Z-103, when the gastric tissue Zn content for Z-103 and ZnSO4 were compared, the Zn content of ZnSO4 was lower than that for Z-103 at both the normal and ulcerous site. In summary, Z-103 shows a long-term adhesive and permeable action on the gastric mucosa in acetic acid ulcer rats, and it has a comparable high affinity at the ulcerous site.

Acetates↗
PubMed1992

[Chronic fatigue syndrome--cases in the Kanebo Memorial Hospital].

In our hospital, 134 patients (28 male, 106 female, 10-82 years of age) were diagnosed as having chronic fatigue syndrome (CFS). Some patients had mild elevation of antibodies against Epstein-Barr Virus and immunologic abnormalities (natural killer cell dysfunction and high rates of skin reactivity to house dust, pollen, drugs and common food). In the patients with immunologic abnormalities, we found decreases in serum concentrations of arachidonic acid and dihomogamma-linolenic acid. A Kampo medicine, Ren-Shen-Yang-Rong-Tang was used in the management of 134 patients and 98 patients returned to work or school.

Adolescent↗
PubMed1992

[Selection of graft materials in case of emergency coronary bypass surgery following failed angioplasty].

The clinical characteristics of selection of graft materials were analysed for patients undergoing emergency coronary artery bypass surgery (CABG) following failed coronary angioplasty (PTCA). Ten emergency CABGs were performed from January 1983 to December 1991. Perioperative variables and follow-up were compared to 18 patients undergoing elective CABG after PTCA. The emergency group had shorter operative time (p less than 0.01) and shorter bypass time (p less than 0.05). Moreover the emergency group had decreased use of the internal thoracic artery (ITA) (40% vs 94.4%, p less than 0.01). There was no use of bilateral ITAs in the emergency group. There was not significant difference in hospital mortality and medium term follow-up between two groups. In conclusion, emergency CABG carries a significantly less use of ITA graft than elective CABG although ITAs are superior to SVGs about long term patency rate. So it is desirable that arterial graft should be used under an appropriate selection at emergency operation.

Aged↗
PubMed1991

Measurement of voltage dependence of capacitance of planar bilayer lipid membrane with a patch clamp amplifier.

The voltage dependence of capacitance was measured by using the setup which was almost the same as that for the study of ion channels. The coefficient which represents the voltage dependence of capacitance itself also changes as a function of the duration of voltage application if hexadecane is contained in bilayer lipid membrane (BLM). The method of Alvarez, O., and R. Latorre (1978. Biophys. J. 21:1-17) was extended to treat BLM with hexadecane.

Alkanes↗
PubMed1991

Clinical effects of nitrendipine on variant angina pectoris.

The clinical effects of nitrendipine, a new calcium antagonist, were investigated in a single-blind test on 21 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during different treatment periods at doses of 10 mg once a day (period I) and 20 mg once a day (period II). The number of anginal attacks decreased significantly from a pretreatment level of 2.1 +/- 0.3 per day to 0.7 +/- 0.2 per day in treatment period I and 0.3 +/- 0.1 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with the observation period before treatment (p less than 0.01, p less than 0.001, respectively). In 20 patients with continuous ECG monitoring, the frequency of ST-segment elevation was 4.5 +/- 1.0 per day during the pretreatment period; it decreased significantly to 0.9 +/- 0.6 per day in treatment period I and 0.5 +/- 0.3 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The duration and the maximum magnitude of ST-segment elevation also improved significantly in both treatment periods. These results demonstrate the efficacy of nitrendipine in the treatment of variant angina at a single daily dose of 10 mg.

Angina Pectoris, Variant↗
PubMed1991

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 1st communication: absorption, distribution, metabolism and excretion after single administration to rats.

Studies on the absorption, distribution, metabolism and excretion of 14C-Z-103 and 65Zn-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) were performed after oral administration to rats. After oral administration of 14C-Z-103 and 65Zn-Z-103, the blood concentrations of 14C-radioactivity were 30- to 40-fold higher than those of 65Zn-radioactivity. The 14C-radioactivity showed a dose-dependent increase of Cmax and AUC values in the dose range from 13.1 mg/kg to 100 mg/kg, and remained longer in the blood. In contrast, no dose-dependent increase of AUC was observed with 65Zn-radioactivity, suggesting saturation of absorption at doses more than 30 mg/kg of 65Zn-Z-103. The major route of excretion of 14C-radioactivity was by excretion into the expired air, amounting to 38.8% of the administered dose, while the urinary and fecal excretions were low values at 4.1% and 13.3%, respectively. The radioactivity remaining in the carcass accounted for 39.3% of the dose. On the other hand, in the case of 65Zn-radioactivity, 85.0% of the administered dose was excreted into the feces and 10.5% of the dose remained in the carcass. Both 14C- and 65Zn-radioactivities were distributed to the whole body, while 14C-radioactivity showed higher concentrations in the body, and was retained longer than the 65Zn-radioactivity. When the plasma and the liver and kidney homogenates, from rats received 14C-Z-103, were treated with trichloroacetic acid (TCA), the radioactivities in the TCA-insoluble fraction increased as a function of time. Following the treatment of the homogenates with protease, the radioactivities in the TCA-insoluble fraction decreased. In vitro study was showed that L-carnosine of 14C-Z-103 added to the homogenates of liver and small intestine was metabolized to L-histidine. The results suggest that the remaining radioactivities in tissues and organs caused the incorporation of the metabolites of 14C-Z-103 into endogenous high molecular substances.

Animals↗
PubMed1991

Study on the metabolic fate of catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc]. 2nd communication: absorption, distribution, metabolism and excretion after repeated administration to rats.

After repeated administration of 14C-Z-103 (catena-(S)-[mu-[N alpha-(3- aminopropionyl)histidinato(2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) to rats for 21 days, the accumulation of radioactivity in the blood and tissues was proportional to the number of doses given. Following treatment of the terminal blood, plasma, liver and kidney samples with trichloroacetic acid (TCA) or protease, the radioactivity in these tissues was demonstrated to be TCA-insoluble and solubilized by the protease treatment. Thus, the accumulation of radioactivity after repeated administration of 14C-Z-103 was considered to be due to the utilization of the metabolites of L-carnosine, the constituent of Z-103, into a protein. The cumulative ratios of radioactivity excreted into the urine, feces and expired air and the radioactivity remaining in the carcass after repeated administration of 14C-Z-103 for 21 days were similar to those values obtained after a single administration, suggesting that repeated administration did not influence the excretion profile of Z-103. During the period of repeated administration of non-radioactive Z-103 to rats for 21 days, the fecal content of zinc was higher than that in nontreated rats, whereas it returned to the control level at 48 h after the final administration. There was no significant difference in the urinary concentration of zinc between treated and non-treated animals during the period of repeated administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗