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Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 451 records · Page 25Linked to original sources

Correlation of the bioavailability of diazepam from uncoated tablets in beagle dogs with its dissolution rate and bioavailability in humans.

The bioavailability of diazepam (I) in uncoated tablets in beagles was tested using tablets tested previously in humans. The correlations of the dissolution rates and bioavailabilities of these tablets in humans and beagles were examined. The plasma level of N-desmethyldiazepam (II), the main metabolite of I, was used as an index of bioavailability after p.o. administration of uncoated tablets of I, because I is rapidly metabolized. Thus the plasma level of I is very low, and AUCs (areas under plasma level-time curves) calculated from plasma levels of II were related to the dose of I (2-10 mg). With different tablets, the rates and extents of bioavailability of I differed significantly in beagles, but only the rate of bioavailability showed significant differences in humans. The rank orders of tablets, based on the blood levels of II soon after p.o. administration of the tablets were the same, but other parameters of bioavailability of I in the tablets were quite different in beagles and humans. Consequently, there was no significant correlation between the bioavailabilities of I in beagles and humans. The gastric fluid of beagles is almost neutral, and the bioavailabilities of the tablets in beagles correlated well with the dissolution rates of I determined at pH 4.6, but not at pH 1.2. The differences in the bioavailabilities of I in humans and beagles were attributed to differences in transit time in the gastrointestinal tract and/or in the volume of the gastrointestinal fluid.

Animals↗

Ordering of mouse immunoglobulin heavy chain genes by molecular cloning.

We have determined the order of the mouse immunoglobulin gamma 1, gamma 2 b, gamma 2 a and epsilon genes by molecular cloning of overlapping chromosomal segments. The results clearly demonstrate that the order is 5'-gamma 1-(21 kilobases)-gamma 2b-(15 kilobases)-gamma 2a-(15 kilobases)-epsilon-3'. There seem to be no J regions at the 5' side of each constant region gene so far obtained except for the mu gene and these constant region genes seem to have repetitive sequences characteristic of switch (S) regions at their 5' side.

Animals↗

Cloning of mouse immunoglobulin epsilon gene and its location within the heavy chain gene cluster.

Mouse immunoglobulin epsilon chain gene was cloned from DNA of a hybridoma producing anti-dinitrophenyl IgE, which was constructed by fusing a spleen cell of a BALB/c mouse with a variant clone of MOPC21 myeloma (IgG1 producer). Because a given active heavy chain constant region (CH) gene is linked to a heavy chain joining segment (JH) gene at its 5' side, the expressed C epsilon gene of the hybridoma was cloned from a phage library containing partial Sau3A digests of IgE hybridoma DNA by using a J gene fragment as a probe. Among 6 X 10(5) phages screened, five positive clones were obtained and three of them were identified as C epsilon gene clones by restriction mapping, Southern blot hybridization, R-loop formation, and partial nucleotide sequence determination. The determined nucleotide sequence predicted the amino acid sequence which resembles a part of the CH3 domain of human epsilon chain. The deletion profile of the C epsilon gene in various myelomas expressing different CH genes indicates that the C epsilon gene is located between the C gamma 2a and C alpha genes. The linkage (5'-epsilon-alpha-3') was directly confirmed by molecular cloning of the overlapping chromosomal segments from newborn mouse DNA.

Animals↗

Rearrangements of immunoglobulin genes during differentiation and evolution.

Immunoglobulin genes are shown to undergo dynamic rearrangements during differentiation as well as evolution. We have demonstrated that a complete immunoglobulin heavy chain gene is formed by at least two types of DNA rearrangement during B cell differentiation. The first type of rearrangement is V-D-J recombination to complete a variable region sequence and the second type is S-S recombination to switch a constant region sequence. Both types of recombination are accompanied by deletion of the intervening DNA segment. Structure and organization of CH genes are elucidated by molecular cloning and nucleotide sequence determination. Organization of H chain genes is summarized as VH-(unknown distance)-JH-(6.5 kb)-C mu-(4.5 kb)-C delta-(unknown distance)-C gamma 3-(34 kb)-C gamma 1-(21 kb)-C gamma 2b-(15 kb)-C gamma 2a-(14.5 kb)-C epsilon-(12.5 kb)-C alpha. The S-S recombination takes place at the S region which is located at the 5' side of each CH gene. Nucleotide sequence of the S region comprises tandem repetition of closely related sequences. The S-S recombination seems to be mediated by short common sequences shared among S regions. A sister chromatid exchange model was proposed as a mechanism for S-S recombination. Comparison of nucleotide sequences of CH genes indicates that immunoglobulin genes have scrambled by intervening sequence-mediated domain transfer during their evolution.

Animals↗

Low-birth-weight and congenital rubella syndrome: effect of gestational age at time of maternal rubella infection.

Birth weights of 42 full-term patients with congenital rubella syndrome were analyzed. All of these infants were products of pregnancies in which the exact dates of the maternal first day of last menstrual period and of the time of onset of the mothers' rubella rash were known. The range of time of maternal rubella associated with low-birth-weight was in the gestational age interval from 16 to 100 days. Low-birth-weight may have a relationship with time of maternal rubella rather than with the type of defects, i.e., cataract, heart disease, and deafness.

Female↗

Lupus erythematosus-like syndrome with selective complete deficiency of C1q.

A 37-year-old Japanese man in previously good health was hospitalized because of swelling of the auricles had discoid erythema of the face. Clinical and laboratory findings satisfied the diagnostic criteria for systemic lupus erythematosus proposed by the American Rheumatism Association. However, serologic studies showed weakly positive antinuclear factor and absence of anti-DNA antibody and lupus erythematosus cells. A striking abnormality was the total absence of serum hemolytic complement activity (CH50). Further studies showed selective complete deficiency of C1q, a subunit of the first component of complement (C1). This is the first reported case of lupus erythematosus-like syndrome with selective complete deficiency of C1q.

Adult↗

Serum lymphocytotoxins and lymphocyte responses to mitogens of Down syndrome person.

Lymphocyte responses to phytohemagglutinin P (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) and incidence of serum lymphocytotoxins in 20 Down syndrome persons were investigated. There was no change in lymphocyte blastogenesis to mitogens in younger Down syndrome individuals (less than 30 years of age) as compared to control persons. The lymphocytes of Down syndrome subjects over 30 years of age showed significantly decreased responses to PHA, Con A, and PWM. Results suggest that with increasing age, Down syndrome persons seem to have an impairment in lymphocyte function. Serum lymphocytotoxins that were not related to age occurred in 4 of the Down syndrome subjects (20 percent). There was no correlation between the presence of lymphocytotoxins and lymphocyte blastogenesis in these subjects.

Adolescent↗

Inverted terminal repeat sequence in the macronuclear DNA of Stylonychia pustulata.

The structure of macronuclear DNA of a hypotrichous ciliate, Stylonychia pustulata, was examined by both electron microscopy and nucleotide sequence analysis. The DNA in the macronucleus consists of small linear molecules with average length of about 3400 base pairs (bp). Most, if not all, of these DNA molecules have identical inverted terminal repeat sequence of 20 nucleotide residues. This sequence is 5'-CCCCAAAACCCC-AAAACCCC.

Animals↗

The differences in purine metabolism between T and B lymphocytes.

In this study enzyme activities involved in purine metabolism were measured in T and B lymphocytes separated by E and EAC rosetting methods. Adenosine deaminase, purine nucleoside phosphorylase and HGPRTase activities were significantly elevated in T cells, compared to the activities in B cells. There were no significant differences in adenosine kinase and APRTase activities between T and B lymphocytes. In contrast, PRPPsynthetase activities were higher in B cells than in T cells. The uptake of various radiolabeled precursors by mitogen stimulated lymphocytes was studied. The uptake of 14C-formate by the mitogen stimulated lymphocytes was markedly lower, compared to that of 14C-adenosine and or 14C-purine bases. The uptake of 14C-adenosine by PHA stimulated lymphocytes was considerably higher than that of Con A or PWM stimulated lymphocytes. However, the uptake of 14C-hypoxanthine into lymphocytes stimulated with PWM was increased by comparison with unstimulated lymphocytes. From these results it seems that adenosine plays a central role in the metabolism of T cells, and that purine bases are preferentially utilized in B cells.

Adenosine Deaminase↗

Immobilization of Escherichia coli cells containing aspartase activity with kappa-carrageenan. Enzymic properties and application for L-aspartic acid production.

Whole cells of Escherichia coli having high aspartase (L-asparate ammonialyase, EC 4.3.1.1) activity were immobilized by entrapping into a kappa-carrageenan gel. The obtained immobilized cells were treated with glutaraldehyde or with glutaraldehyde and hexamethylenediamine. The enzymic properties of three immobilized cell preparations were investigated, and compared with those of the soluble aspartate. The optimum pH of the aspartase reaction was 9.0 for the three immobilized cell preparations and 9.5 for the soluble enzyme. The optimum temperature for three immobilized cell preparations was 5--10 degrees C higher than that for the soluble enzyme. The apparent Km values of immobilized cell preparations were about five times higher than that of the soluble enzyme. The heat stability of intact cells was increased by immobilization. The operational stability of the immobilized cell columns was higher at pH 8.5 than at optimum pH of the aspartase reaction. From the column effluents, L-aspartic acid was obtained in a good yield.

Ammonia-Lyases↗

Immobilization of enzymes and microbial cells using carrageenan as matrix.

Conditions for the gelation k-carrageenan, which is a new polymer for immobilization of enzymes and microbial cells, were investigated in detail. k-Carrageenan was easily induced to gel by contact with metal ions, amines, amino acid derivatives, and water-miscible organic solvents. By using this property of k-carrageenan, the immobilization of enzymes and microbial cells was investigated. Several kinds of enzymes and microbial cells were easily immobilized with high enzyme activities. Immobilized preparations were easily tailor-made to various shape such as cube, bead, and membrane. The obtained immobilized preparations were stable, and columns packed with them were used for continuous enzyme reaction for a long period. Their operational stabilities were enhanced by hardening with glutaraldehyde and hexamethylenediamine.

Amidohydrolases↗