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Biomedical subjects

T Honjo

Publications and source records attributed to T Honjo.

At least 361 records · Page 20Linked to original sources
PubMed1984

[Clinical experience on sulbactam/cefoperazone in the pediatric field].

Approximately 20 mg/kg/day of sulbactam/cefoperazone (SBT/CPZ) was given by one shot intravenous injection to 16 pediatric inpatients with respiratory tract infections (13 cases), urinary tract infection (1 case), skin infection (1 case) or gastrointestinal tract infection (1 case). An excellent efficacy in 6 cases and a good efficacy in 10 cases were observed. Causative organisms were not identified in the respiratory tract infections, even though the efficacy was excellent or good. Side effects were not noticed in particular and SBT/CPZ was judged as safe enough agent. Concentrations of SBT/CPZ in the spinal fluid were determined in 3 patients. Their low concentrations suggested the poor transfer into the spinal fluid. Finally, SBT/CPZ is a very useful agent since it is effective also against resistant organisms which produce penicillinase-type beta-lactamases.

Adolescent↗
PubMed1984

[Bacteriological, pharmacokinetic and clinical studies on sulbactam/cefoperazone in the pediatric field].

Bacteriological and clinical effect of a newly developed SBT/CPZ in the treatment for pediatric patients was assessed by a study group consisting of 15 institutions. The results were as follows. Antibacterial effect Susceptibility studies were performed with 93 clinical isolates. The MIC of SBT/CPZ was one-tube inferior or almost similar to that of CPZ in susceptible organisms. In CPZ-resistant organisms at the inoculum of 10(8) cells/ml, however, SBT/CPZ was much superior to CPZ on the basis of the MIC. When the MIC of SBT/CPZ was compared to that of CPZ in 27 strains which have high beta-lactamase-producing activity, it was found that many of CPZ-resistant organisms were susceptible to SBT/CPZ. Serum concentration and urinary excretion The serum concentrations of SBT and CPZ were 33.2 micrograms/ml, respectively at 15 minutes after 20 mg/kg SBT/CPZ was administered by intravenous bolus injection, and those of SBT and CPZ, 51.0 micrograms/ml and 108.3 micrograms/ml, respectively following 40 mg/kg SBT/CPZ therapy. The serum concentrations of CPZ were 2.1-2.4 times as high as those of SBT. The concentrations were dose-related. The half-lives of SBT and CPZ following 20 mg/kg SBT/CPZ administration were 0.94 hour and 1.50 hours, respectively, and those following 40 mg/kg SBT/CPZ were 0.95 hour and 1.53 hours, respectively. There was no significant difference between 20 mg/kg and 40 mg/kg administrations. When compared between SBT and CPZ, CPZ had slightly longer half-lives. At the termination of 1 hour drip infusion of 20 mg/kg SBT/CPZ, the serum concentrations of SBT and CPZ were 16.7 micrograms/ml and 40.1 micrograms/ml, respectively. In the case of 40 mg/kg, the levels of SBT and CPZ were 38.6 micrograms/ml and 94.9 micrograms/ml, respectively. The concentrations were found to be dose-related as were following intravenous bolus injections. The SBT half-lives obtained after 20 mg/kg and 40 mg/kg SBT/CPZ administrations were 1.39 hours and 0.89 hour, respectively; those of CPZ, 2.00 hours and 1.44 hours, respectively. The highest urinary concentration occurred 0-2 hours after intravenous bolus injections of 20 mg/kg or 40 mg/kg SBT/CPZ. Urinary excretion of SBT over 6 hours was 60.0% and 67.7%, and that of CPZ, 21.2% and 25.0%, indicating higher urinary excretion for SBT. When 20 mg/kg SBT/CPZ or 40 mg/kg was administered over 1 hour by drip infusion, urinary excretion became the highest at 1-3 hours after administration. Urinary excretion of SBT over 7 hours following 20 mg/kg and 40 mg/kg SBT/CPZ was 68.8% and 80.3%, respectively, and that of CPZ, 24.4% and 27.3%. The results were similar to those observed following intravenous bolus injections.

Adolescent↗
PubMed1984

Duplicated immunoglobulin gamma 2a genes in wild mice.

The Japanese wild mouse, Mus musculus molossinus, has duplicated immunoglobulin gamma 2a genes, whereas most of the laboratory-strain mice have single gamma 2a genes. This duplication provides a unique system in which molecular mechanisms of the evolutionary rearrangement of the immunoglobulin gene can be studied. For this purpose it is important to elucidate the organization of the immunoglobulin genes surrounding the duplicated gamma 2a genes. It is also interesting to assess the distribution of this haplotype among the wild mouse population. Partially overlapping chromosomal segments that encompass the gamma 2b, gamma 2a-1, gamma 2a-2, and epsilon genes were isolated from phage libraries containing DNA fragments from M. m, molossinus. The organization of this region has been elucidated as 5'-gamma 2b-(18 kb)-gamma 2a-1-(19 kb)-gamma 2a-2-(14 kb)-epsilon-3'. Both gamma 2a-1 and gamma 2a-2 genes have their own switch regions in the 5' flanking region. Two homology units of 13 kb, each containing the gamma 2a gene, were identified. The homology units alternate with repetitive sequences of low homology, making the location of the recombination site obscure. Seventeen of 31 Japanese and Chinese wild mice screened had duplicated gamma 2a genes, indicating a wide distribution of this genetic event in the Asian wild mouse population. Moreover, three alleles each of the gamma 2b and gamma 2a loci have been observed in this small sample population. An unequal crossing-over event between heterologous haplotypes is proposed to account for the duplication of the gamma 2a gene, and a candidate for one member of the pair was identified among wild mouse haplotypes. These results suggest that the immunoglobulin heavy-chain gene family of the Japanese and Chinese wild mouse subspecies has accumulated not only polymorphic divergence due to point mutations, but also dynamic rearrangements such as gene duplication, during its recent evolution since divergence of these subspecies from the European subspecies about one million years ago.

Animals↗
PubMed1984

Immunoglobulin gene organization of ultraviolet-illuminated human lymphoblastoid cell lines producing both IgM and IgG.

We have studied the immunoglobulin gene organization of ultraviolet light (u.v.)-induced variant cells derived from an Epstein-Barr virus-transformed cell line. One variant produced IgG1 and two variants produced both IgM and IgG1 whereas the parental cell line produced IgM. Southern blot analyses of DNAs of these cells revealed a newly rearranged JH fragment in all the variants. The newly rearranged JH fragment also hybridized with the C gamma 1 sequence. The mu and gamma 1 chains produced in the double isotype-producing variants share the same VH sequence. u.v. illumination also induced rearrangement of the C lambda gene in the IgG1-producing variant. The double isotype producers contained the immunoglobulin gene organization and mutation best explained by fusion of the IgG1 producer and the parental IgM producer.

Amino Acid Sequence↗
PubMed1983

The D-JH complex is an intermediate to the complete immunoglobulin heavy-chain V-region gene.

We have examined the organization of the immunoglobulin JH segments in three clones derived from a single Abelson murine leukemia virus-transformed cell. Cloning and nucleotide sequence analyses of the JH-containing fragments have revealed the rearrangement from the preformed D-JH complex to the complete VH-D-JH gene, which was accompanied by the expression of the intra-cytoplasmic mu chain. In one case a JH segment downstream to the preformed D-JH was used to create a new VH-D-JH gene. Upon the D-JH and VH-D-JH rearrangements the intervening D segments were deleted from the chromosome. One of the expressed VH genes suffered from a large deletion of the 3' portion (including the 95th cysteine residue) of the VH segment. We discuss the possible mechanism of the allelic exclusion.

Abelson murine leukemia virus↗
PubMed1983

Common terminal repeats of the macronuclear DNA are absent from the micronuclear DNA in hypotrichous ciliate, Stylonychia pustulata.

Comparison of nucleotide sequences of a macronuclear DNA and its micronuclear counterpart of a hypotrichous ciliate, Stylonychia pustulata, demonstrates that common terminal repeats (C4A4) of the macronuclear DNA are not present at the corresponding region in the micronuclear genome. The results indicate that the common terminal C4A4 repeat is added or translocated during or after the rearrangement of the micronuclear DNA to the macronuclear DNA.

Animals↗
PubMed1983

Expression of human immunoglobulin E epsilon chain cDNA in E. coli.

Using the cDNA of human epsilon chain, three expression plasmids that code directly the constant portion of the epsilon chain (C epsilon 1-C epsilon 4, C epsilon 2-C epsilon 4 and C epsilon 3-C epsilon 4 domains) were constructed. These epsilon chain peptides were synthesized in E. coli under the control of the trp promoter-operator. The bacterially produced peptides have the antigenicity of human epsilon chain and gave the molecular weights equal to the values calculated from the amino acid sequence of the constructed plasmids.

Base Sequence↗
PubMed1983

Molecular cloning and nucleotide sequencing of human immunoglobulin epsilon chain cDNA.

DNA complementary to mRNA of human immunoglobulin E heavy chain (epsilon chain) isolated and purified from U266 cells has been synthesized and inserted into the PstI site of pBR322 by G-C tailing. This recombinant plasmid was used to transform E. coli chi 1776 to screen 1445 tetracycline resistant colonies. Nine clones (pGETI - 9) containing cDNA coding for the human epsilon chain were recognized by colony hybridization and Southern blotting analysis with a nick-translated human IgE genome fragment. The nucleotide sequence of the longest cDNA contained in pGET2 was determined. The results indicate that the sequence of 1657 nucleotides codes for 494 amino acids covering a part of the variable region and all of the constant region of the human epsilon chain. Most of the amino acid sequence deduced from the nucleotide sequence is in substantial agreement with that reported. Furthermore a termination codon after the -COOH terminal amino acid marks the beginning of a 3' untranslated region of 125 nucleotides with a poly A tail. Taking this into account, the structure of the human epsilon chain mRNA, except a part of the 5' end, is conserved fairly well in the cDNA insert in pGET2.

Amino Acid Sequence↗
PubMed1983

Structure of the human immunoglobulin C epsilon 2 gene, a truncated pseudogene: implications for its evolutionary origin.

Cloning of the overlapping DNA fragments together with Southern hybridization experiments showed the organization of the human C epsilon and C alpha gene cluster as 5'-C epsilon 2-14 kilobases-C alpha 1----C epsilon 1-13 kilobases-C alpha 2-3'. Comparison of the nucleotide sequences of the C epsilon 1 and C epsilon 2 genes revealed that four deletions have taken place in the C epsilon 2 gene and its flanking regions. The three deleted regions in the 5' side of the C epsilon 2 gene are partially filled with shorter inserted sequences. One of them has removed the CH1 and CH2 exons and a portion of the epsilon switch (S epsilon) region. The S epsilon region and the CH4 exon still retain the functional structures, whereas the CH3 exon has been inactivated by deleting its 5' intervening sequence necessary for splicing. The tetranucleotide T-G-G-G (or T-G-G-C), which is usually found in close proximity of the class-switch recombination sites in mouse myelomas, is located 5' to the three deletion sites. The results imply that the mechanism responsible for the heavy chain class-switch recombination might be relevant to the evolutionary mechanism of creation of the truncated C epsilon 2 gene. The other deletion in the 3' flanking region of the C epsilon 2 gene may be due to slipped mispairing of the short direct repeat (C-C-C-C-C) at both ends.

Base Sequence↗
PubMed1983

Multiple DNA fragment polymorphisms associated with immunoglobulin mu chain switch-like regions in man.

DNA probes containing the switch region (S) associated with the human immunoglobulin heavy chain mu gene were used to investigate polymorphisms in the germ-line human DNA. Six polymorphisms, detected by a single restriction enzyme (Sst I) are described. Linkage studies in 29 families show that five of the six polymorphisms, although relatively unassociated in random individuals, segregate in complete linkage one to the other and to Gm allotypes (markers on the heavy chain of IgG), while the sixth segregates independently. Altogether, when one considers the DNA markers at the five closely linked loci and the IgG1 and IgG3 heavy chain allotypes, 33 different haplotypes have been described; of these, 28 are detected by the DNA polymorphism alone. Study of 158-187 random haplotypes showed strong linkage disequilibrium only between one DNA polymorphism (Sst A) and Gm. Of the polymorphic Sst I loci, one, Sst E [associated with 2.2- to 2.7-kilobase (kb) fragments], is included in the mu chain S region (S mu); another, Sst A (6.8-7.4 kb), must be very close to the gamma 1-gamma 3 chain gene cluster. Based on studies of an IgE human myeloma, a third polymorphism, Sst C (4.8-5.5 kb), should map 3' of the active epsilon chain gene. An Sst I restriction enzyme map of phage clones carrying the two alpha chain genes indicates that Sst A and Sst C loci probably overlap with the alpha 1 and alpha 2 S regions, respectively. Both deletion/duplications and point mutations were detected.

Chromosome Deletion↗
PubMed1983

Escherichia coli extract-catalyzed recombination in switch regions of mouse immunoglobulin genes.

We have shown that Escherichia coli extracts catalyze recombination between mouse immunoglobulin mu and alpha genes inserted separately in lambda phage vectors carrying different genetic markers. Most of the recombination sites in the inserts are located in the switch regions of the heavy chain genes, as previously found in the expressed genes of myeloma cells. The recombination took place at relatively high frequency (10(-4)). The recombinational system in E. coli or lambda phage seems to prefer short nucleotide sequences similar to those used in the class switch recombination.

Animals↗
PubMed1983

Origin of adult T-cell leukemia virus. Implication for its zoonosis.

Adult T-cell leukemia virus (ATLV) is a retrovirus infecting man. The ATLV genome consists of long terminal repeat (LTR), gag, pol, env and pX sequences and does not carry a typical v-onc gene. The function of the pX sequence is unknown. To search for the origin of ATLV, segments of the ATLV genome were hybridized to DNAs of various species. The sequences homologous to the pX region of ATLV are represented in the genomes of mouse and rat but not in other species including primates and the human. Neither the pol nor U3 sequence of LTR is conserved in any cellular DNA examined. Sequences slightly homologous to the U3R sequence are found in rabbit, chicken and Xenopus. The results suggest that the pX sequence of ATLV might have derived from rodents. Since ATLV can infect primates, rabbit and rat, ATLV might have been prevalent among a wide variety of mammals and exchanged genetic segments (zoonotic) like influenza virus. If we assume that the original host of ATLV is a rodent rather than man, the pX sequence is homologous to host cellular sequences and reminiscent of the v-onc gene although the function of the pX sequence is not clear.

Animals↗
PubMed1982

Immunoglobulin switch region-like sequences in Drosophila melanogaster.

We found immunoglobulin switch (S) region-like sequences in DNAs of wide variety of organisms including sea urchin, yeast and Drosophila that do not produce immunoglobulins. DNA fragments carrying Smu-like sequences were cloned from Drosophila and the nucleotide sequence of a clone is almost identical to that of the mouse Smu region. Restriction fragments of Drosophila Smu-like sequences and their flanking regions seem to vary among Drosophila species. Possible evolutionary significance of the Smu-like sequence in invertebrates was discussed.

Animals↗
PubMed1982

Nucleotide sequences of switch regions of immunoglobulin C epsilon and C gamma genes and their comparison.

Immunoglobulin class switch involves a unique recombination event that takes place at the switch (S) region which is located 5' to each constant region (C) gene of the heavy (H) chain. For example, differentiation of the B lymphocyte from a mu-chain producer to an epsilon-chain producer is mediated by the switch recombination between the S mu and S epsilon regions. In order to elucidate the molecular mechanism for the switch recombination, we have determined nucleotide sequences surrounding the class switch recombination sites of the C epsilon and C gamma 3 genes and those in the 5' flanking regions of the C gamma 2a and C delta genes. The results indicate that the 5' flanking regions of all the CH genes except for the C delta gene contain the S regions which comprise tandem repetition of short unit sequences in agreement with the previous analyses of the S gamma 1, S gamma 2b, S mu, and S alpha regions. Comparison of the nucleotide sequences of all the S regions revealed that length as well as nucleotide sequences of the S regions vary among different classes of the CH gene, but they share short common sequences, (G)AGCT and TGGG(G). The nucleotide sequence of the S mu region is homologous to those of the other S regions in the decreasing order of the S epsilon, S alpha, S gamma 3, and (S gamma 1, S gamma 2b, s gamma 2a) regions. We have compared the nucleotide sequences immediately adjacent to the recombination sites of seven rearranged genes and have always fund tetranucleotides TGAG and/or TGGG, except for one case. Such tetranucleotides may constitute a part of the recognition sequence of a putative recombinase. These results provide further support for our previous proposal that the switch recombination may be facilitated by short common sequences dispersed in all the S regions.

Animals↗