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Biomedical subjects

S Ohno

Publications and source records attributed to S Ohno.

At least 901 records · Page 50Linked to original sources
PubMed1982

The interactions of androgen receptor with poly(A)-containing RNA and polyribonucleotides.

The androgen receptor from mouse kidney cytosol binds not only to DNA but also to RNA as assayed by competition with DNA-cellulose centrifugation or by direct binding with agarose-polynucleotides. The dihydrotestosterone-receptor complex interacts more strongly to poly(A)-containing mRNA than to native natural DNA; it binds much more tightly to synthetic poly(G) than to natural DNA and other homopolyribonucleotides such as poly(U), poly(A), or poly(C). Poly(U) is moderately effective in competing for the complex, whereas poly(A) and poly(C) re not effective. Competition studies with heteropolyribonucleotides show that polymers containing G are most effective on binding to the androgen receptor, whereas those containing U are moderately effective, and those containing only A and C are least effective. Several analogues of poly(G), such as poly(X), poly(I), and poly(m7G) interact very well with the dihydrotestosterone-receptor with some differences in the bindings. A double-stranded polymer, poly(I) . poly(C) competes poorly for the androgen receptor. The observations that the androgen receptor binds to RNA and interacts with polyribonucleotides selectively suggest that androgen receptor-RNA interaction could play important roles in gene regulation.

Animals↗
PubMed1982

Inducer-responsive expression of the cloned human interferon beta 1 gene introduced into cultured mouse cells.

A hybrid plasmid was constructed from pSV2-Ecogpt (Mulligan and Berg, 1981) and the cloned 1.8 kilobase chromosomal DNA segment which contains the human interferon (HIFN-beta 1) gene and its flanking sequences. Cultured mouse FM3A cells were transfected by the hybrid plasmid and several Ecogpt+ clones were selected. Southern blot analysis of the DNA from these mouse cell clones showed that two of them contained a few copies of the 1.8 kilobase human DNA. Synthesis of mRNA characteristic of the HIFN-beta 1 mRNA increased as measured by RNA blot analysis when those clones were treated with Newcastle disease virus or with poly(I):poly(C). In addition, the induced mouse cell clones gave rise to the synthesis of human IFN-beta 1. These results suggest the presence of a unique nucleotide sequence in the 1.8 kilobase DNA which is sufficient for the inducer-responsive expression of the human IFN-beta 1 gene.

Animals↗
PubMed1982

Close association of HLA-Bw51 with Behçet's disease.

Frequency of HLA-A, B, and C antigens was studied in 184 patients with Behçet's disease to investigate the immunogenetically determined predisposition to this disease. A statistically significant increased incidence of HLA-B5 or Bw51 was noted in the patients as compared with the normal control subjects. No significant difference was observed in the distribution of other HLA antigens. On the basis of HLA studies, it seems likely that the susceptibility genes to Behçet's disease closely linked to HLA-Bw51 may have been spread by the old nomadic tribes or the Turks via the Silk Route.

Behcet Syndrome↗
PubMed1982

Nerve growth factor, laminin, and fibronectin promote neurite growth in human fetal sensory ganglia cultures.

The effect of mouse nerve growth factor (NGF) on cultured human fetal sensory neurons was assayed by measuring neurite length, density and rate of growth. Addition of NGF increased adhesion of dissociated sensory neurons cultured on collagen coated surfaces. Almost all neurons of 9 to 10 week old fetuses are postmitotic, contain neuron-specific enolase, (an enzyme linked to differentiation), and require NGF for optimal neurite growth. Sensory ganglia re-explanted on collagen showed maximal neurite length and density when treated with 1 ng/ml of NGF. Neurite density was reduced considerably in the absence of mouse NGF and was almost abolished by addition of antimouse NGF antibodies. Surfaces coated with the matrix glycoproteins laminin or fibronectin further stimulated neurite growth of ganglia in the presence of NGF. Increasing amounts of matrix proteins could partly compensate for the absence of mouse NGF or the inhibition of NGF activity by antibodies. Stimulation of neurite growth by matrix proteins was time-dependent, and neurites showed maximum length at 10 days (2 to 3 mm). Neurite growth was more pronounced with laminin than with fibronectin and collagen, and antibodies to laminin suppressed all neurite growth. In the presence of a constant amount of NGF, mean neurite growth reached 26 microns/hr (at 1 day), and was 2.1 and 1.7 times faster on laminin and fibronectin (respectively) than on collagen. Thus, laminin, and to a lesser degree fibronectin, may enhance neurite growth of human sensory neurons in synergy with NGF.

Cell Adhesion↗
PubMed1982

Nucleic acid synthesis in proliferating peroxisomes of rat liver as revealed by electron microscopical radioautography.

Thirty albino rats were fed with a diet containing 1, 2 or 4% di-(2-ethylhexyl)-phthalate (DEHP), a peroxisome-proliferating agent. Others were fed with normal diet as controls. Both groups were sacrificed at varying intervals from 3 days to 4 weeks. The livers were either removed and fixed in glutaraldehyde and osmium tetroxide or fixed in glutaraldehyde, incubated in a diaminobenzidine (DAB) medium, postfixed, embedded in Epon, and sectioned. Other tissues were incubated in Eagle's MEM containing either [P3H-thymidine or [3H]uridine, fixed, embedded in Epon, sectioned, and radioautographed. Specimens were observed in a Hitachi H-700 electron microscope. The number of peroxisomes showing DAB reactivity increased in DEHP-fed animals as compared with normal controls. In radioautograms of normal rats labelled with [3H]thymidine, no silver grains were observed, whereas grains were observed overt some nuclei, mitochondria and peroxisomes of DEHP-fed animals. In contrast, radioautograms of tissue labelled with [3H]uridine revealed a few grains in nuclei and mitochondria or endoplasmic reticulum of normal rats, although grains appeared in nuclei, mitochondria, endoplasmic reticulum and peroxisomes of DEHP-fed animals more frequently. From these results, it is concluded that [3H]thymidine and [3H]uridine were incorporated in the proliferating peroxisomes, suggesting that nucleic acid synthesis had taken place.

Animals↗
PubMed1982

Ocular manifestations of Kawasaki's disease (mucocutaneous lymph node syndrome).

In a prospective study of the ocular manifestations of Kawasaki's disease (mucocutaneous lymph node syndrome) in 18 children (11 boys and seven girls, ranging in age from 5 months to 9 years), we found bilateral injection of the bulbar conjunctiva in 16, bilateral iridocyclitis in 14, superficial punctate keratitis in four, vitreous opacities in two, papilledema in two, and subconjunctival hemorrhage in one. Conjunctival injection and iridocyclitis were always bilateral, and fellow eyes always had the same degree of inflammation. There were significant correlations between ocular inflammation and erythrocyte sedimentation rate (P less than .0001) and C-reactive protein level (P less than .0009). No serious ocular complications occurred.

Blood Sedimentation↗
PubMed1982

Mouse immunoglobulin coding sequences for the heavy-chain variable region arose as repeats of the two short building blocks.

The coding sequence for the 97-amino-acid-residue-long immunoglobulin heavy-chain variable (VH) regions of the mouse apparently arose as repeats of the two short building blocks. Three of the recognizable copies of the one 21-base-long prototype sequence A-C-T-G-G-A-T-A-T-G-A-C-C-T-G-G-A-G-T-G-G are invariably found to occupy the fixed positions within the 5' half of each VH coding sequence. Interestingly, the first and third copies specify the relatively invariant regions represented by the 7th to 13th and 41st to 47th amino acid residues (the first and second framework regions), whereas the second copy specifies the first hypervariable region (31st to 35th amino acid residues). These copies maintain at least 57.2% (12 out of 21) base sequence homology to the above-noted prototype building block. Base sequences of the other 14- to 15-base-long prototype building block differ from each other by as much as 60% between individual VHS. Yet one of its copies invariably occupies the terminal region of each VH coding sequence, thus specifying the very invariant third framework region. Other copies occupy unfixed positions in the VH and its attendant hydrophobic leader coding sequence as well as in adjacent noncoding sequences. The homology thus revealed between the VH coding sequence and its adjacent noncoding sequences suggests their concordant evolution.

Amino Acid Sequence↗
PubMed1982

Base sequence of a cloned snake W-chromosome DNA fragment and identification of a male-specific putative mRNA in the mouse.

A 2.5-kilobase fragment of a sex-specific satellite DNA from the Colubrid snake species Elaphe radiata has been cloned, and its sequence has been determined. It contains 26 and 12 copies, respectively, of two base quadruplets, G-A-T-A and G-A-C-A, as its sole highly repetitious elements. Southern hybridization experiments with genomic DNA of the chicken, the mouse, and man indicated male sex-specific conservation of at least parts of this cloned DNA. In situ hybridization experiments with metaphase chromosomes of the mouse showed that elements that can cross-hybridize with parts of the cloned snake DNA are concentrated in the pericentric region of the Y chromosome. In blot hybridization experiments with liver poly(A)+ polysomal RNAs of male and female mice, a probe consisting of the first 1,224 bases of the cloned snake DNA singled out a male-specific RNA of 1,250-1,400 bases. Inasmuch as the proximal end of this probe contained an open reading frame (44 consecutive amino acid-specifying codons), the male-specific putative mRNA so detected may specify H-Y antigen. By contrast, a probe consisting of bases 1,480-1,906, containing the simple repeats of the quadruplets, singled out a shorter (approximately 1,000-base) RNA from males and females alike. Although this RNA is poly(A)+, we have yet to establish its attachment to ribosomes.

Animals↗
PubMed1982

Identification of the 45-base-long primordial building block of the entire class I major histocompatibility complex antigen gene.

Within the 885-base-long incomplete coding sequence for the mouse class I major histocompatibility complex (MHC) antigen H-2Kb heavy chain, we have identified 32 recurring base oligomers (1 decamer, 4 octamers, 9 heptamers, and 18 hexamers), the decamer being T-C-A-C-C-C-T-G-A-G. The compilation of these recurring base oligomers led to the identification of the 45-base-long primordial building block for this class of genes which is: C-C-T-G-C-G-G-A-C-A-A-T-G-T-C-A-C-C-C-T-G-A-G-C-T-G-C-T-G-G-G-C-T-C-T-G-G-G-C-G - T-T-G-A-C. Inasmuch as these base oligomers that recurred within the mouse H-2Kb coding sequence proper also recurred within the adjacent, transcribed noncoding sequence, we conclude that the entire approximately equal to 4,000-base-long germ-line DNA segment containing eight or nine separate exons of the coding sequence for class I MHC antigen heavy chains can be construed as having evolved from tandem repeats of this one 45-base-long primordial building block.

Amino Acid Sequence↗
PubMed1982

Identification of the 48-base-long primordial building block sequence of mouse immunoglobulin variable region genes.

Mouse immunoglobulin heavy-chain variable region (Ig VH) genes apparently arose from the approximately 600-base-pair-long (approximately 12 tandem repeats of the 48-base-pair-long primordial building block sequence TTC-AGC-AGC-CTG-ACT-GGA-TAT-GAC-CTG-GAG-TGG-ACT-TAC-TGC-GCA-AGA) that in the original reading frame specified the amino acid sequence Phe-Ser-Ser-Leu-Thr-Gly-Tyr-Asp-Leu-Glu-Trp-Thr-Tyr-Cys-Ala-Arg. The previously identified, shorter prototype building blocks merely represented particular portions of the above primordial sequence. Even today, the direct descendant in toto of this primordial sequence specifies the last one-sixth of each VH coding sequence: the 83rd to 98th amino acid residues. Furthermore, its four truncated derivatives specify the 4th to 14th, 17th to 23rd, 29th to 37th, and 38th to 48th amino acid residues. Accordingly, all three relatively invariant--therefore, conserved--framework regions (FW-1, FW-2, and FW-3) of VHs are specified by recognizable--therefore, conserved--descendants of the primordial sequence.

Amino Acid Sequence↗
PubMed1982

The 48-base-long primordial building block of immunoglobulin light-chain variable regions is complementary to the primordial building block of heavy-chain variable regions.

The ancestral gene for immunoglobulin light-chain variable regions (Ig VLs) of the kappa as well as the lambda class apparently arose from about 12 tandem repeats of the 48-base-long primordial building block sequence TCT-TGC-GCA-GTA-AGT-CCA-CTC-CAG-GTC-ATA-TCC-AGT-CAG-GCT-GCT-GAA. Even today, amino acid residues 67 to 82 of each Ig V kappa L are still specified by a direct descendant in toto of the above-noted primordial building block, whereas amino acid residues 14 to 25 are invariably specified by its truncated copy. The Ig VL primordial building block presently identified is 100% complementary to the Ig VH (heavy-chain variable region) primordial building block previously identified. In the recognition of specific antigenic determinants by antibodies, Ig VL and Ig VH of light-chain--heavy-chain dimers have to complement each other. It is perhaps fitting that the primordial building blocks of the two are represented by the complementary strands of the same 48-base-pair-long DNA sequence.

Animals↗
PubMed1982

Detection of gamma interferon in the sera of patients with Behçet's disease.

The serum levels of interferon (IFN) in 58 patients with Behçet's disease were significantly higher than those in 79 normal controls (P less than 0.0001). The average IFN titer was 51.4 +/- 9.3 IU/ml in the patients and 5.9 +/- 1.1 IU/ml in the controls. The patients were then divided into two groups according to the stage of ocular disease. Forty-six patients in the ocular convalescent stage had higher IFN levels (61.3 +/- 11.2 IU/ml) than did 12 patients in the exacerbation stage (13.2 +/- 3.0 IU/ml). Moreover, the kinetics of the IFN level in the circulation of seven patients showed a significant decrease of IFN in the exacerbation stage. IFN activity in sera from patients was destroyed by acid treatment and heating at 56 degrees C for 30 min and was not neutralized with anti-human IFN-alpha and -beta sera. In addition, it was demonstrated that vesicular stomatitis virus inhibitors detected in sera from both the patients and the controls had no effect on our IFN assay. Therefore, antiviral activity detected in sera of patients seems to be due to gamma interferon (IFN-gamma). IFN-gamma may play a significant role in the pathophysiology of Behçet's disease.

Adolescent↗
PubMed1982

Studies on spontaneous production of gamma-interferon in Behçet's disease.

Gamma-interferon (IFN-gamma) is detected at a higher level in the sera of patients with Behçet's disease than in control subjects. To investigate the cellular source of IFN-gamma, peripheral blood lymphocytes (PBL) from patients were cultured and found to produce IFN-gamma spontaneously in their fresh culture fluids. The average IFN titers in cultures of the patients' PBL were significantly higher than those of the control cultures (p less than 0.0001). The IFN activity was significantly higher in cultures of the patients in the ocular convalescent stage than in the exacerbation stage (p less than 0.0001), as was the case with serum interferon activity. Fractionation of PBL showed that only T gamma lymphocytes of the patients produced IFN-gamma spontaneously in the cultures. No IFN was produced in the culture fluids of T non-gamma cells, non-T cells or macrophages. T gamma cells and IFN-gamma may therefore play a significant role in the immunopathophysiology of Behçet's disease.

Behcet Syndrome↗
PubMed1982

Evolution is condemned to rely upon variations of the same theme: the one ancestral sequence for genes and spacers.

Nature is condemned to play variations of the same theme in evolution, past commitments progressively restricting freedom of choices in evolutionary directions. While each family of genes evolved by the mechanism of gene duplication, this mechanism is extremely inefficient, the usual fate of redundant copies of the ancestral gene being degeneracy. As a result, the euchromatic DNA of higher organisms became a desert in which still-functioning genes are found scattered like oases at an average distance of 35,000 base-pairs of barren stretch between neighbors in the case of mammals. The 20-base-long sequence (AGCTG) (AGCTG) (AGCTG) (GGGTG) can be considered as one of the few ultimate ancestors of all euchromatic DNAs. Long stretches of intergenic spacers are mostly represented by degenerate subfamilies of repeats derived from the above. Certain 30- 50-base-long units of such degenerate subfamilies apparently served as the primordial building block of the ultimate ancestor of each family of genes. For example, the primordial building block of the ancestor for antigen-binding sites (variable regions) of mammalian immunoglobulin heavy chains apparently was TTC-AGC-AGC-CTG-ACT-GGA-TAT GAC-CTG-GAG-TGG-ACT-TAC-TGC-GCA-AGA, which is the original reading frame specified in the 16-amino-acid-residues-long sequence Phe-Ser-Ser-Leu-Thr-Gly-Tyr-Asp-Leu-Glu-Trp-Thr-Tyr-Cys-Ala-Arg.

Base Sequence↗
PubMed1982

Effects of diethyldithiocarbamate (DDC), fusaric acid, catecholaminergic and serotonergic receptor blockers on the ascending pathway from the ventrolateral part of the medulla oblongata.

The effect of a potent inhibitor of dopamine-beta-hydroxylase, diethyldithiocarbamate (DDC) or fusaric acid, on the antidromically evoked potentials by electrical stimulation of the preoptic suprachiasmatic area (POSC) was examined. Thirty seven neurons in the ventrolateral part of medulla oblongata (VLMO) were successfully tested after DDC injection. Nineteen of them decreased in amplitude to approximately 50% of control levels at 120 min after DDC injection, 20% at 180 min. These 19 neurons were characterized by having a notch in the rising phase and taking a longer time to complete the initial deflection. After fusaric acid injection, ten neurons in the VLMO were successfully tested and four of them decreased in amplitude similar to DDC injection. Effects of receptor blockers of noradrenaline, dopamine and serotonin on the single unit responses of the POSC neurons to the VLMO stimulation in proestrous rats were examined in order to know which of noradrenaline, dopamine or serotonin are involved in the neural transmission from the VLMO to the POSC. After the injection of phenoxybenzamine, an alpha-adrenergic receptor blocker, the rates of facilitatory and inhibitory responses in the POSC neurons to the VLMO stimulation were significantly decreased. Percentages of facilitatory and inhibitory responses were not changed significantly after injection of pimozide, a dopaminergic receptor blocker, or methysergide, a serotonergic receptor blocker. These findings suggest that noradrenaline might be involved in the transmission of the VLMO stimulation effect on the POSC neurons and that VLMO noradrenaline-containing neurons send their axons directly to the POSC.

Action Potentials↗