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T Kakutani

Publications and source records attributed to T Kakutani.

At least 55 records · Page 3Linked to original sources
PubMed1990

Coding strategy of rice stripe virus: major nonstructural protein is encoded in viral RNA segment 4 and coat protein in RNA complementary to segment 3.

The two major proteins found in plants infected with rice stripe virus (RSV), coat protein and a major nonstructural protein (major NS), were purified and their partial amino acid sequences were determined. Oligonucleotides were synthesized according to the amino acid sequence information, and used as probes for Northern blot analyses of four single-stranded RNA species (segments 1-4) and four double-stranded RNA species of RSV. The results indicated that the coding strategy of RSV was similar to those of ambisense viruses: Segment 3 coded for the coat protein in the (-) sense while segment 4 coded for the major NS protein in the (+) sense.

Amino Acid Sequence↗
PubMed1990

Sequence analysis and product assignment of segment 7 of the rice dwarf virus genome.

The complete nucleotide sequence of segment 7 of the rice dwarf virus (RDV) genome was determined. The segment was 1696 bp long and its plus-strand terminal sequence, 5'GGCAAA---UGAU3', was in agreement with the consensus sequence previously found in other segments of RDV. A 10 bp inverted repeat was found adjacent to the termini. A single long open reading frame extended for 1518 bp from the first AUG triplet (positions 26 to 28), and encoded a polypeptide of 506 amino acids (Mr 55,339). This protein had 32% identity in the amino acid sequence to the 57K protein encoded by segment 7 of the wound tumour virus genome. The translation product of transcript RNA made from 'tailored' cDNA of RDV segment 7 comigrated with the 60K core protein of RDV in 10% polyacrylamide gel and reacted with antiserum against the 60K core protein of RDV. Segment 7 of the RDV genome therefore codes for the 60K core protein.

Amino Acid Sequence↗
PubMed1990

Ambisense segment 4 of rice stripe virus: possible evolutionary relationship with phleboviruses and uukuviruses (Bunyaviridae).

The complete nucleotide sequence of segment 4 of the rice stripe virus (RSV) genome was determined from overlapping cDNA clones and by direct RNA sequencing. The segment has two long open reading frames (ORFs). One of the ORFs (534 bases) is in the 5' region of the viral sequence, and the other (858 bases) is in the viral complementary sequence of the viral 3' region. Such ambisense genome organizations have been seen previously in RNAs of phleboviruses, uukuviruses and arenaviruses. The ORF in the viral sequence encodes the major non-structural protein, but the product of the ORF in the viral complementary sequence (Mr 32407) has not yet been identified. The first 18 bases of each of the 5' and 3' ends of segment 4 are complementary in sequence. Among the 3'-terminal 16 bases, 14 were identical between RSV genome segments 3 and 4. These terminal sequences are very similar to those of RNAs of phleboviruses and uukuviruses. These and other characteristics indicate a possible evolutionary relationship between RSV and phleboviruses and/or uukuviruses.

Amino Acid Sequence↗
PubMed1990

The pharmacokinetic pattern of glycosylated human recombinant lymphotoxin (LT) in rats after intravenous administration.

We have examined the pharmacokinetics of glycosylated recombinant human lymphotoxin (LT) after intravenous bolus injection in rats and compared them with those of tumor necrosis factor (TNF) or LT species. The results are as follows. 1) The mean half-life of glycosylated LT in serum increases for each increase in dose, and the distribution volume (V) and total body clearance [(Cl (total)] tend to decrease for increase in dose. On the other hand, the half-life of TNF also increases for increase in dose, but the V tends to increase for increase in dose and Cl (total) does not change. 2) The glycosylated LT distributes to all organs so far tested except brain, and tends to accumulate to kidney more than other tissues at 6 h after the injection. 3) Nonglycosylated LT produced by E. coli and the glycosylated LT species carrying both N-type and mucin-type sugar moieties (25 kDa LT) have shorter half-lives and higher Cl (total)s than 23 kDa LT carrying N-type sugar moieties alone. The 21 kDa LT, the same species as 23 kDa LT except that it lacks 15 amino acid residues at the N-terminus, disappears much faster than 23 kDa LT and shows higher V and Cl (total). Thus, glycosylated LT shows nonlinear pharmacokinetics like TNF, but the deposition is quite different from that of TNF. The high serum concentration of glycosylated LT depends upon the presence of N-type sugar moieties, but not mucin-type sugar moieties. The N-terminal protein chain of LT also correlates with the serum concentration.

Amino Acids↗
PubMed1990

Comparison of human lymphotoxin gene expression in CHO cells directed by genomic DNA or cDNA sequences.

Four recombinant plasmids coding for human lymphotoxin (LT) were constructed with genomic DNA (gDNA) or cDNA sequences. The simian virus 40 (SV40) early region, which contains the early promoter, an intron of the small-t-antigen-encoding gene, and polyadenylation signal sequences, was used for transcriptional and post-transcriptional regulatory elements in the construction of these plasmids. Two of them contained gDNA and the other two contained cDNA. One of the gDNA plasmids and one of the cDNA plasmids carry the SV40 intron between the structural gene and polyadenylation signal. Transient and stable gene expression levels of these plasmids in Chinese hamster ovary (CHO) cells were measured by assaying the secreted LT. The plasmid carrying gDNA without the SV40 intron was expressed more efficiently than the other three plasmids in both transient and stable gene expression assays.

Animals↗
PubMed1989

Statistical moment analysis of hepatobiliary transport of phenol red in the perfused rat liver.

A new experimental system was applied to study hepatobiliary transport of drugs. Rat livers were perfused using a single-pass technique, and phenol red was momentarily introduced to this system from the portal side. Outflow dilution patterns of phenol red were analyzed using statistical moment theory, and kinetic parameters of hepatic distribution and elimination of phenol red were calculated from moments, namely, the hepatic extraction ratio (Ei) and elimination rate constant (kel,i). A larger distribution volume (Vi) was obtained for phenol red than for 131I-human serum albumin (HSA) and 51Cr-red blood cells (RBC), indicating its extravascular diffusivity. The biliary excretion of conjugated phenol red was delayed relative to that of the free agent. The larger biliary mean transit time (tbile,conj.) represents the processes of biliary transport and intrahepatic metabolism. Further, the effects of dose and perfusion temperature on the hepatobiliary transport of phenol red were determined. With high doses or low perfusion temperatures (20 and 27 degrees C), Ei, kel,i, and intrinsic clearance (CLint,i) of phenol red and biliary recovery of free and conjugated phenol red (Fbile,free, Fbile,conj) significantly decreased. The temperature-dependent and saturable processes in hepatic uptake, metabolism, and biliary excretion of phenol red were assessable to moment analysis.

Animals↗
PubMed1988

Cell behavior during formation of prestalk/prespore pattern in submerged agglomerates of Dictyostelium discoideum.

When cells dissociated from Dictyostelium discoideum slugs were cultured in roller tubes, they formed agglomerates in which prestalk cells were initially dispersed but soon sorted out to the center and then moved to the edge to reconstitute the prestalk/prespore pattern. To examine the mechanism of sorting out, individual prestalk cells were traced by a videotape recorder. The radial component of the rate of movement toward the center of the presumptive prestalk region was calculated. Prestalk cells did not move randomly, but rather directionally toward the center. Their movement was pulsatile, with a period of ca. 15 min, and accompanied by occasional formation of cell streams, thus resembling the movement observable during cell aggregation. These results favor the idea that prestalk cells sort out to the prestalk region due to differential chemotaxis rather than differential adhesiveness. After formation of the prestalk/prespore pattern, the prestalk region rotated along the circumference of the agglomerates. This appears comparable to migration of slugs on the substratum, the rate of rotation being similar to that of slug migration. To examine the processes of pattern formation during development, washed vegetative cells were cultured in roller tubes. Prespore cells identified by antispore immunoglobulin initially appeared randomly within the agglomerates, but then nonprespore cells accumulated in the center and finally moved to the edge to establish the prestalk/prespore pattern, the processes being similar to those of pattern reconstruction with differentiated prestalk and prespore cells.

Cell Aggregation↗
PubMed1988

Effect of plasma protein binding on drug disposition in muscle tissue: application of statistical moment analysis and network theory to in situ local single-pass perfusion system.

The local disposition characteristics of mitomycin C (MMC) and five lipophilic prodrugs in rabbit hind leg muscle were examined using an in situ single-pass perfusion experiment. Test compounds inputted into a perfusion line as a rectangular function (unit pulse) were perfused with or without albumin and their outflow patterns were analyzed by statistical moment analysis. In interpretation of statistical moment parameters, the well-stirred model was applied to the local perfusion system based on the plate theory of a chromatographic system and some general pharmacokinetic parameters (the disposition parameters) were derived from the moments. A new theory which elucidates the relationships among the moments for plasma protein binding, unbound (free), and total drug fraction was established based on network theory. Using this system, the following conclusions were made for mitomycin C and its five lipophilic derivatives: (i) In the absence of albumin, an increase in lipophilicity led to an increase in organ clearance and distribution volume; (ii) drug bound to albumin did not transfer to the extravascular space; (iii) in the presence of albumin, an increase in lipophilicity results in a decrease in clearance.

Animals↗
PubMed1987

Disposition characteristics of mitomycin C-dextran conjugate in normal and tumor-bearing muscles of rabbits.

Disposition characteristics of the macromolecular prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), in normal and tumor (VX2 carcinoma)-bearing rabbit thigh muscles were studied using the in situ vascular perfusion technique. Three types of cationic MMC-D (MMC-Dcat) and two types of anionic MMC-D (MMC-Dan) with different carrier molecular weights were used. After bolus arterial injection in normal muscles, 83-96% of injected MMC-D was recovered in the venous outflow regardless of the carrier size or charge, whereas less than 60% of MMC was recovered in the same system. By applying statistical moment analysis to the outflow pattern of these drugs, pharmacokinetic parameters representing their disposition characteristics were obtained. Smaller intrinsic clearance (CLint) and distribution volume (V) were noted for MMC-D than for MMC, indicating low extravascular diffusion of MMC-D. In the tumor-bearing muscle, blood contamination from other parts of the body increased and a shortage of flow recovery due to the neovascularization of the tumors occurred. The disposition parameters of MMC-Dcat with a molecular weight of 500,000 (T-500) indicated some tissue distribution and sequestration in the tumor preparation. After constant infusion of [14C]MMC-D (T-500) for 4 h, tissue radioactivity concentrations were determined in various tissues. A higher radioactivity was observed in the viable region of the tumor and the lymph node compared with the normal muscle tissue and the necrotic region of the tumors. 131I-Labeled human serum albumin also gave similar results. In conclusion, higher tumor localization of antitumor agents may be made possible by the application of macromolecular prodrugs.

Animals↗
PubMed1986

Characterization of liposomes and an emulsion containing mitomycin C or lipophilic mitomycin C prodrugs.

The characteristics of liposomes and an oil-water emulsion containing either mitomycin C (MMC) or its lipophilic prodrugs were investigated. Prodrugs were incorporated into liposomes and oil droplets of an oil-water emulsion, and this incorporation was dependent on the lipid content of the liposomes and droplets. A good correlation was observed between the calculated lipid:water partition ratios and partition coefficients in chloroform:water. The prodrugs were rapidly distributed between the lipid and aqueous phases when they were injected into the dispersion medium of empty liposomes and an oil-water emulsion, or when the formulations incorporating prodrugs were diluted with water. Addition of prodrugs to liposomes containing perylene resulted in a decrease of fluorescence. Based on these findings, prodrugs were concluded to be incorporated into lipidic dispersion formulations based on their partitioning behavior. N1a-[(Nonyloxy)carbonyl]MMC (7) showed the highest incorporation into lipidic formulations, while prodrugs with moderate lipophilicities were rapidly released from lipid particles. Liposomes incorporating 7 maintained their multilamellar vesicular form as shown by electron microscopy and by examining their entrapping capacity for water soluble marker dyes. The release of prodrug 7 from both formulations was slow in a buffer solution, but considerable release and conversion to the parent drug were observed when rat plasma was added to the same system. These results suggest that the stability of MMC could be improved by incorporation into lipidic formulations and that a suitable release rate in vivo could be accomplished by use of a prodrug.

Chemical Phenomena↗
PubMed1985

A new method for assessment of drug disposition in muscle: application of statistical moment theory to local perfusion systems.

A new experimental system is used to determine exact information concerning local drug disposition. Rabbit hind leg is perfused in situ using a single-pass technique, and outflow curves of drugs are analyzed using statistical moment theory. By the introduction of chromatographic concepts and the application of the well-stirred model to the local perfusion system, physiologically and/or physicochemically meaningful parameters are derived from the first three moments. Moreover, in the assessment, drug disposition is divided into elimination and distribution. The elimination process is also evaluated with respect to rate and extent. This system is used to elucidate the disposition characteristics of mitomycin C and its lipophilic derivative nonyloxycarbonyl mitomycin C.

Animals↗
PubMed1985

Absorption characteristics of the lipophilic prodrug of mitomycin C from injected liposomes or an emulsion.

Mitomycin C (MMC) is amphiphilic and so cannot be incorporated into lipoidal delivery systems. To develop a lipoidal delivery system, its prodrug, nonyloxycarbonyl MMC, was formulated in liposomes and in o/w emulsions and the usefulness of these formulations was evaluated. After injection into the rat thigh muscle, MMC was rapidly absorbed regardless of the dosage form. However, the prodrug was retained at the injection site for considerably longer when formulated in a lipid dispersion system. The accumulation of MMC at regional lymph nodes was also investigated and whereas free MMC arrived at and disappeared from the lymph nodes almost immediately after injection, the prodrug arrived at an early stage and its concentration decreased only gradually, remaining fairly high 2 h after injection. Liposomal lipids appeared to accumulate at the lymph nodes to a greater degree than o/w emulsions. It is suggested that the combination of lipidic carrier devices with lipophilic prodrugs may be a useful adjunct to cancer chemotherapy.

Absorption↗
PubMed1984

[Primary malignant lymphoma of the spleen in a long surviving patient and review of the literature].

A case of primary malignant lymphoma of the spleen is presented. The tumor was successfully removed and eight years after the surgery, the patient died without any recurrence of the malignant lymphoma. A review of the literature, with special reference to prognosis is also presented. Long-term follow-up is necessary in patients with primary malignant lymphoma of the spleen who have been curatively operated because the malignant lymphoma of the spleen may in fact be a metastatic lesion from nodal and extranodal lymphomas, or may be a partial lesion from a multicentrically originating lymphoma.

Humans↗