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K Ikehara

Publications and source records attributed to K Ikehara.

At least 19 recordsLinked to original sources
PubMed2002

Origins of gene, genetic code, protein and life: comprehensive view of life systems from a GNC-SNS primitive genetic code hypothesis.

We have investigated the origin of genes, the genetic code, proteins and life using six indices (hydropathy, alpha-helix, beta-sheet and beta-turn formabilities, acidic amino acid content and basic amino acid content) necessary for appropriate three-dimensional structure formation of globular proteins. From the analysis of microbial genes, we have concluded that newly-born genes are products of nonstop frames (NSF) on antisense strands of microbial GC-rich genes [GC-NSF(a)] and from SNS repeating sequences [(SNS)n] similar to the GC-NSF(a) (S and N mean G or C and either of four bases, respectively). We have also proposed that the universal genetic code used by most organisms on the earth presently could be derived from a GNC-SNS primitive genetic code. We have further presented the [GADV]-protein world hypothesis of the origin of life as well as a hypothesis of protein production, suggesting that proteins were originally produced by random peptide formation of amino acids restricted in specific amino acid compositions termed as GNC-, SNS- and GC-NSF(a)-0th order structures of proteins. The [GADV]-protein world hypothesis is primarily derived from the GNC-primitive genetic code hypothesis. It is also expected that basic properties of extant genes and proteins could be revealed by considerations based on the scenario with four stages.

Amino Acids↗
PubMed2001

Transfer of heme oxygenase 1 cDNA by a replication-deficient adenovirus enhances interleukin 10 production from alveolar macrophages that attenuates lipopolysaccharide-induced acute lung injury in mice.

By using a direct, intratracheal inoculation of an adenovirus encoding heme oxygenase 1 (Ad.HO-1), model gene therapy for acute lung injury induced by inhaled pathogen was performed. Data demonstrated that Ad.HO-1 administration is as effective as the pharmacologic upregulation of the endogenous HO-1 gene expression by hemin to attenuate neutrophilic inflammations of the lung after aerosolized lipopolysaccharide (LPS) exposure. Interestingly, immunohistochemical analysis revealed that the HO-1 gene was transferred not only to the airway epithelium, but to the alveolar macrophages (AMs). Moreover, overexpression of exogenous HO-1 in the macrophages provided a high level of endogenous interleukin 10 (IL-10) production from the macrophages, and additional experiments using IL-10 knockout mice demonstrated that the increase in IL-10 in the macrophages was critical for the resolution of neutrophilic migration in the lung after LPS exposure. These results suggest that AMs not only are barriers for efficient gene transfer to the respiratory epithelium, but also represent logical targets for Ad-mediated, direct, in vivo gene therapy strategies for inflammatory disorders in humans.

Adenoviridae↗
PubMed1997

Longitudinal study of the mental health of caregivers caring for elderly patients with dementia: effect of institutional placement on mental health.

One hundred and three family caregivers of relatives with dementia were longitudinally surveyed to examine the course of caregivers' mental health after the relatives had been placed in full-time care facilities. Mental health was assessed twice, with a 6-month interval, using the Japanese version of the 60-item General Health Questionnaire. The degree of social dysfunction was significantly reduced within 6 months after placement, while the other indicators of mental health (e.g. anxiety-insomnia, depression, somatic symptom and psychiatric morbidity) were not reduced within this term. However, anxiety-insomnia and psychiatric morbidity were significantly reduced more than 6 months after placement. Analyses by caregivers' lineal relations to the relatives indicated that only daughters-in-law showed a significant decrease in anxiety-insomnia and a marginal reduction in psychiatric morbidity. This study suggests that caregivers' social dysfunction was more greatly reduced than anxiety-insomnia and psychiatric morbidity within a relatively short term after placement, and that its effects on mental health might vary with the lineal relations.

Adult↗
PubMed1997

[Primary pulmonary lymphoma diagnosed from monoclonality of lymphocytes in a transbronchial biopsy specimen].

A 57-year-old man was found on a routine chest X-ray examination to have three infiltrative shadows: two in the right lung field and one in the left. Examination of a transbronchial biopsy specimen revealed infiltration of many small lymphocytes under the bronchial mucosa. In situ hybridization showed that they were monoclonal, and primary pulmonary lymphoma was diagnosed. The patient also had liver cirrhosis, diabetes mellitus, and hypertension. He was treated with a combination of pirarubein, cyclo-phosphamide, vindesine, prednisolone, and etoposide, but the tumors did not shrink. Therefore, as of the time of this writing he was being given only etoposide.

Biopsy↗
PubMed1997

[Pleural B cell lymphoma presenting as paraplegia].

A 54-year-old man felt pain on the right side of his chest. Two months later, paraplegia developed. A chest CT scan revealed a pleural effusion and a mass lesion along the right parietal pleura. The lesion extended directly into the adjacent part of the spinal canal and compressed the spinal cord. Cytologic examination of the pleural effusion revealed atypical lymphoid cells, and examination of a transcutaneous biopsy specimen showed monotonous atypical B lymphocytes. The diagnosis was pleural malignant lymphoma. Chemotherapy induced a partial remission, but 14 months after the first examination he died of central nervous system involvement. Pleural lymphoma can directly compress the spinal cord and cause paraplegia. Early diagnosis and therapy greatly affect the outcome in patients with spinal cord compression.

Humans↗
PubMed1996

A possible origin of newly-born bacterial genes: significance of GC-rich nonstop frame on antisense strand.

Base compositions were examined at every position in codons of more than 50 genes from taxonomically different bacteria and of the corresponding antisense sequences on the bacterial genes. We propose that the nonstop frame on antisense strand [NSF(a)] of GC-rich bacterial genes is the most promising sequence for newly-born genes. Reasons are: (i) NSF(a) frequently appears on the antisense strand of GC-rich bacterial genes; (ii) base compositions at three positions in the codon are nearly symmetrical between the gene having around 55% GC content and the corresponding NSF(a); (iii) amino acid compositions of actual proteins are also similar to those of hypothetical proteins from the GC-rich NSF(a); and (iv) proteins from NSF(a) of 60% or more GC content are flexible enough to adapt to various molecules encountered as novel substrates, due to the high glycine content. To support our proposition, using a computer we generated hypothetical antisense sequences with the same base compositions as of NSF(a) at each base position in the codon, and examined properties of resulting proteins encoded by the imaginary genes. It was confirmed that NSF(a) of GC-rich gene carrying about 60% GC content is competent enough for a newly-born gene.

Amino Acids↗
PubMed1996

[Eosinophilic pneumonia presenting as a mass shadow].

A 35-year-old man underwent routine chest roentgenography and a mass shadow was seen in the left lung field. Examination of a transbronchial lung biopsy specimen revealed that many eosinophils had infiltrated under the bronchial mucosa and into the alveolar septum. The total serum IgE concentration was high, and skin tests with Aspergillus antigen and serum precipitating antibodies against Aspergillus were positive. The mass lesion disappeared without any therapy, and a cystic lesion remained. Mediators released from eosinophils were thought to have damaged the lung tissue. We should have administrated corticosteroids as soon as possible.

Adult↗
PubMed1993

Guanylate kinase of Escherichia coli K-12.

We have identified the gene gmk, in the same operon as rpoZ, spoT, and recG at about 82 minutes on the Escherichia coli chromosome. The gmk (GMP kinase) gene encodes a peptide of 23,592 Da, possessing extensive similarity to the amino acid sequence of guanylate kinase from yeast. To confirm that gmk truly encodes guanylate kinase and to explore some of its enzymatic features, we have overproduced the product of gmk and purified it to homogeneity. Unlike guanylate kinases purified from eukaryotic sources, E. coli guanylate kinase is multimeric, and ionic conditions dictate its protomeric state; under low ionic conditions it appears to be a tetramer while under high ionic conditions it is a dimer. Kinetic analysis reveals that guanylate kinase, again, unlike eukaryotic guanylate kinases, binds GMP cooperatively and that the observed cooperatively changes with ionic strength. These results indicate that, despite extensive sequence similarity to its eukaryotic counterparts, E. coli guanylate kinase is structurally and enzymatically different.

Amino Acid Sequence↗
PubMed1993

Unusually biased nucleotide sequences on sense strands of Flavobacterium sp. genes produce nonstop frames on the corresponding antisense strands.

From investigation of eight Flavobacterium sp. genes encoding enzyme proteins, it was found that six genes had nonstop frames (NSFs) on the antisense strands, and base sequences of the genes are mainly composed of repeating triplet sequence(s), 5'-GNC-3' (where G and C are guanine and cytosine, and N is either of the four bases), in the reading frames. Thus, we concluded that the biased nucleotide sequences on the sense strands produce NSFs on the corresponding antisense strands. Furthermore, from the precise alignments of both nucleotide and amino acid sequences of two related Flavobacterium sp. genes, nyIB and nyIB', it was found that base replacements might have occurred symmetrically in the codons. That is, transversions between G and C were observed at high frequencies at the first and third positions of codons, but not at the second positions. At the first position, AG base transitions were observed much more than similar CT transitions, whereas CT transitions were found at the third positions at a relatively high frequency. These suggest that symmetrical base replacements in codons might be the main contribution to evolution in Flavobacterium sp. genes.

Amidohydrolases↗
PubMed1993

[A case of cervico-mediastinal tuberculous lymphadenitis].

A 27-year-old female presented to our hospital because of anterior chest pain and left cervical tumor. Her chest X-ray film showed bilateral swelling of the superior mediastinum, which was composed of multiple mediastinal masses with obliteration of adjacent mediastinal fat on chest CT film. A specimen obtained from a left cervical lymph node histologically showed granuloma formation with central caseous necrosis, and the diagnosis of cervicomediastinal tuberculous lymphadenitis was therefore made. Both cervical tumor and mediastinal masses decreased in size following antituberculous chemotherapy. Mediastinal tuberculous lymphadenitis in young adults is rare. It is difficult to differentiate this condition from other mediastinal tumors, although its CT findings are characteristic.

Adult↗
PubMed1991

Residual guanosine 3',5'-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations.

It was known previously that 1) the relA gene of Escherichia coli encodes an enzyme capable of guanosine 3',5'-bispyrophosphate (ppGpp) synthesis, 2) an uncharacterized source of ppGpp synthesis exists in relA null strains, and 3) cellular degradation of ppGpp is mainly due to a manganese-dependent ppGpp 3'-pyrophosphohydrolase encoded by the spoT gene. Here, the effects of spoT gene insertions and deletions are compared with analogous alterations in neighboring genes in the spo operon and found to be lethal in relA+ strains as well as slower growing in relAl backgrounds than delta relA hosts. Cells with null alleles in both the relA and spoT genes are found no longer to accumulate ppGpp after glucose exhaustion or after chelation of manganese ions by picolinic acid addition; the inability to form ppGpp is reversed by a minimal spoT gene on a multicopy plasmid. Strains apparently lacking ppGpp show a complex phenotype including auxotrophy for several amino acids and morphological alterations. We propose that the SpoT protein can either catalyze or control the alternative pathway of ppGpp synthesis in addition to its known role as a (p)ppGpp 3'-pyrophosphohydrolase. We favor the possibility that the SpoT protein is a bifunctional enzyme capable of catalyzing either ppGpp synthesis or degradation.

Alleles↗
PubMed1989

Characterization of the spoT gene of Escherichia coli.

The Escherichia coli spoT gene encodes a guanosine-3',5'-bispyrophosphate (ppGpp) 3'-pyrophosphohydrolase known to be responsible for cellular (ppGpp) degradation. The DNA sequence of the spoT region is presented. The spoT gene is deduced to be 702 codons long, with a probable UUG initiation codon, and a deduced mass of 79,342 daltons. Two spoT mutations (spoT202 and spoT203) have been localized to an open reading frame by complementation of function as well as by genetic marker rescue. The ability to overexpress the spoT gene is limited, but enough ppGppase activity can be made to reverse ppGpp accumulation during the stringent response to amino acid starvation. The spoT gene is located within a larger spo operon and is flanked by two smaller genes. The first gene in the operon encodes omega, a protein that copurifies with RNA polymerase (Gentry, D. R., and Burgess, R. R. (1986) Gene (Amst.) 48, 33-40). The spoT gene is the second gene in the operon; it is followed by a third open reading frame deduced to encode a protein with a mass of 25,343 daltons. Insertion of a kanamycin resistance gene in the omega gene reduces spoT gene expression as judged by lowered ppGppase activity, relA-dependent reduction of growth rate, and abolition of spoT mutant complementation activity. These effects are reversed by expression of the spoT gene, but not the omega gene, in trans. Transcription of the spo operon occurs in a clockwise direction on the E. coli chromosome and is probably directed by at least two promoters.

Alleles↗
PubMed1985

Induction of stringent response by streptomycin in Bacillus subtilis cells.

A stringent response was induced in Bacillus subtilis vegetative cells by streptomycin. This was confirmed as follows: In B. subtilis stringent cells (BR16S), stable RNA synthesis was repressed, and pppGpp and ppGpp were transiently synthesized in the presence of required amino acids and streptomycin. However, these phenomena were not observed in the isogenic relaxed strain (BR16R) under the same conditions. On the other hand, tetracyclines did not induce the response, and, moreover, the stringent response to streptomycin upon pretreatment of the stringent cells with the antibiotics was released.

Amino Acids↗
PubMed1982

Induction of Bacillus subtilis sporulation by decoyinine and the concomitant disappearance of ppGpp in vegetative cells.

Sporulation of Bacillus subtilis, growing exponentially in the presence of rapidly metabolizable nutrients, was induced by addition of decoyinine (an antibiotic inhibitor of GMP synthesis), and intracellular amounts of ppGpp were determined after 2 M formic acid extraction by polyethyleneimine (PEI)-cellulose thin-layer chromatography. Consequently, it was found that the ppGpp in vegetative cells abruptly disappeared after the addition of decoyinine. This indicates that the disappearance of ppGpp is closely correlated to the initiation of B. subtilis sporulation.

Adenosine↗
PubMed1981

Presence of guanosine 5'-diphosphate 3'-diphosphate in Bacillus subtilis vegetative cells.

Extracts of Bacillus subtilis vegetative cells with 2 M formic acid contained a large amount of a hyperphosphorylated nucleotide ("spot 4" nucleotide). The compound always comigrated with authentic guanosine 5'-diphosphate 3'-diphosphate (ppGpp) on two-dimensional polyethyleneimine (PEI)-cellulose thin-layer chromatography performed with three different solvent systems. Furthermore, all dephosphorylated 32P-labeled derivatives from the "spot 4" nucleotide comigrated on a one-dimensional PEI-cellulose plate with those from authentic ppGpp present in the same reaction mixture, when the compounds were hydrolyzed with snake venom phosphodiesterase or alkali. The level of the "spot 4" nucleotide (ppGpp) in the cell extracts was 0.14 nmol P/A660, corresponding to about one-third of the guanosine 5'-triphosphate (GTP) level and about 10% of the adenosine 5'-triphosphate (ATP) level. These results indicate that a "magic spot" nucleotide, ppGpp, is present at a high level in B. subtilis cells vegetatively growing in mNSMP.

Bacillus subtilis↗
PubMed1981

Disappearance of guanosine 5'-diphosphate 3'-diphosphate in Bacillus subtilis vegetative cells upon carbon source deprivation.

Bacillus subtilis was grown in a nutrient medium, mNSMP, and a synthetic medium, mS6(C), in which spore formation was initiated after vegetative growth and exhaustion of carbon source or glucose. The amounts of intracellular phosphorylated compounds were analyzed at intervals by 2 M formic acid extraction and polyethyleneimine (PEI)-cellulose thin-layer chromatography followed by autoradiography. A hyperphosphorylated nucleotide, guanosine 5'-diphosphate 3'-diphosphate (ppGpp), was accumulated in cells during vegetative growth in both mNSMP and mS6(C), and then the nucleotide was degraded upon initiation of sporulation in both cases. Furthermore, after the nucleotide had disappeared in cells cultivated in mS6(C) upon exhaustion of the carbon source, it could be reformed in the sporulating cells by addition of glucose to the medium. These results suggest that the ppGpp in vegetative cells may function in the regulation of B. subtilis sporulation.

Bacillus subtilis↗