Poly(adenosine diphosphate ribose).
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Biomedical subjects
Publications and source records attributed to H Okazaki.
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Escherichia coli easily developed resistance to a new antimicrobial agent of the sideromycin group, No. 216, by spontaneous mutation. Most of the No. 216-resistant mutants tested proved not to be cross-resistant to E. coli phages T1, T5, and ø80. On the other hand, these phage-resistant mutants were cross resistant to No. 216. The initial site for binding of No. 216 to the sensitive cells was located, at the ton A gene product (Ton A-protein) of the outer membrane. However, unlike the phage-resistant mutants, ton A protein (78K-protein) in most No. 216-resistant mutants was intact and these mutants were possessed a particular 87K protein in the outer membrane. It is suggested that No. 216 is taken up by ton A protein and then penetrates into the cell by way of a particular transport system and that a highly mutable portion may exist in this reaction system.
Sodium borohydride in ethanol solution under mild conditions brings about the stepwise reduction of the 7-keto and the 11-keto groups of rutamycin and the oligomycins to the corresponding hydroxyl groups without further alterations of the macrocyclic lactone structure or other features of the molecule. The reduced compounds, as well as the parent antibiotics, inhibit the ADP-dependent (state 3) respiration, and the Pi formation and proton extrusion that are linked to ATP hydrolysis, but have no effect on other respiration-linked activities in intact rat liver mitochondria. Analogous inhibitory effects of borohydride-treated antibiotics are also observed in rat-liver submitochondrial particles. The reduced compounds are less potent inhibitors than the parent antibiotics. The reduced compounds are more efficient as inhibitors of Pi formation stimulated by conventional uncouplers (e.g. 2,4-dinitrophenol), than of Pi formation stimulated by certain amine-fluorescamine modifiers (e.g.) the benzylamine-fluorescamine compound. In contrast, the parent antibiotics are unable to discriminate between uncoupler-stimulated and modifier-stimulated Pi formation. It is suggested that rutamycin and the oligomycins bind to H+-ATPase as a result of hydrogen bonding to, at least, the 7-keto and/or the 11-keto groups of the antibiotics. When these keto groups are reduced to hydroxyl groups the hydrogen-bonding is less efficient due to the pronounced directional characteristic of hydrogen-bonding to keto groups.
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A strain of actinomycetes, isolated from a soil sample, has produced a novel antibiotic (C11H14O2S) containing a unique thiolactone moiety in its molecule. On the basis of taxonomic studies the producing organism was identified as belonging to the genus Nocardia. The antibiotic, named thiolactomycin, exhibits a broad antibacterial spectrum and particularly potent activity against Salmonella, Serratia and Bacteroides. Furthermore, the acute toxicity is weak in experimental animals. These results indicate that thiolactomycin is distinct from other known antibiotics and represents a new type of antibiotic.
Thiolactomycin is a new broad-spectrum antibiotic, active in vitro against many species of Gram-positive cocci, Enterobacteriaceae, Haemophilus, acid-fast bacteria and anaerobic bacteria. However, the activity is generally moderate and bacteriostatic in action. This antibiotic eludes cross resistance with any of the known antibacterial drugs such as ampicillin, carbenicillin or cycloserine. The effect on Gram-negative bacilli in vitro is little affected by the inoculum size, the presence of horse serum, the pH of the medium or the type of medium. When thiolactomycin was added to the assay medium, the minimum inhibitory concentration of ampicillin against inducible beta-lactamase producing strains of Staphylococcus aureus and Pseudomonas aeruginosa was reduced. Thiolactomycin inhibited the production of inducible beta-lactamase in several organisms.
The new thiolactone antibiotic, thiolactomycin, is rapidly absorbed in rats when administered either orally or by intramuscular injection. A peak in concentration of the drug is reached in the blood and in various visceral organs within 15 minutes after administration. The concentration decreases rather rapidly and about 51-69% of the drug is excreted in urine during the first 24 hours. Though the in vitro effect of thiolactomycin is moderate, it effectively protected mice challenged intraperitoneally with several strains of S. marcescens and K. pneumoniae and more effective than carbenicillin in treating experimental acute urinary tracts infected with S. marcescens. Also, in mice whom immunodefense was decreased by treatment with cyclophosphamide, thiolactomycin was more effective than carbenicillin against S. marcescens challenge.
A new antibiotic, cyanocycline A, was isolated from the fermentation broth of Streptomyces flavogriseus strain No. 49, a soil isolate. The molecular formula of cyanocycline A was determined to be C22H26N4O5. The antibiotic has a cyano group and a N-heterocyclic quinone moiety in its structure. Cyanocycline A was found to have broad spectrum antimicrobial and antitumor activity.
Angioendotheliomatosis is a rare, often disseminated proliferation of malignant intravascular cells of presumed endothelial origin. The disease may primarily affect the cerebral vasculature and lead to confusing symptoms and signs that often defy accurate clinical diagnosis.
Antibody formation was monitored after buffy-coat transfusions were given at weekly intervals for 9 weeks or a single injection of buffy-coat pooled from ten different donors was given. Among patients with no prior transfusion history, 7 patients given repeated transfusions did not develop warm B or T cytotoxins. Among 25 patients receiving pooled buffy-coat, only 1 patient (who had 3 prior pregnancies) developed warm B and T cytotoxins. In contrast, approximately one fourth of patients who had prior blood transfusions developed warm B and T cytotoxins with either repeated or pooled buffy-coat transfusions. We conclude that buffy-coat from 10 donors given weekly or as a single pooled injection does not produce warm B and T cytotoxins in nontransfused patients, but does function as a secondary stimulus in primed patients.
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Histologic features of an invasive mediastinal tumor found in a 25-year-old woman fulfilled the accepted criteria for diagnosis of predominantly lymphocytic thymoma. Histochemical and cell marker studies indicated that the neoplasm contained a preponderance of T lymphocytes. After surgical debulking of the mass, aggressive radiotherapy and chemotherapy eradicated all evidence of thoracic disease. However, six months after the initial diagnosis, rapid development of cranial nerve and brainstem metastases--without detectable recurrent disease elsewhere--resulted in the patient's death. Autopsy examination revealed the presence of peripheral nerve metastases as well. A review of the literature disclosed fewer than 10 cases of central nervous system metastasis from thymoma. In only two of these were there clinicopathologic features similar to those seen in this case.
The incidence of primary intracranial neoplasms in Rochester, Minn, from 1935 through 1977 is reviewed with regard to whether the tumor was diagnosed because of symptoms arising before death or was found incidentally at autopsy. Among males, the overall age-adjusted incidence rate of cases diagnosed before death was 8.3 per 100,000 population per year, which included a rate of 4.0 for gliomas, 1.2 for meningiomas, and 1.5 for pituitary tumors. Among females, the comparable overall rate was 10.1; that included a rate of 4.1 for gliomas, 2.6 for meningiomas, and 1.7 for pituitary tumors. Of all autopsies on subjects aged 55 years and over, about 1% confirmed or discovered gliomas and slightly more than 1% confirmed or discovered meningiomas.
Two different preparations isolated from beef cerebrum have been used to compare the polyadenosine diphosphate ribose (polyADPR) polymerase activities in neuronal and glial nuclei: (1) nuclear suspensions (with or without DNase I treatment), and (2) 1 M NaCl nuclear extracts (soluble enzyme). The DNAse I treatment of nuclei and the solubilization of polyADPR polymerase by 1 M NaCl enhances the polyADPR polymerase activity. The polyADPR polymerase activity is similar in neuronal and glial nuclear suspensions, while the neuronal soluble enzyme activity is significantly higher than that of the glial soluble enzyme. Evidence is presented that the difference in soluble enzyme activities is not due to the effects of DNA or degrading enzymes. Some activating factor(s) seem to be present in neuronal soluble extracts, while both inhibiting and activating factor(s) seem to be present in glial soluble extracts.
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The diameter histograms of cell bodies (cytons) in motor neuron columns at the L5 segment of the spinal cord of adult man reproducibly yield three peaks of increasing height: small (Cs), intermediate (Ci), and large (Cl). Histograms of L5 myelinated axons obtained from the ventral root have two peaks of increasing height: intermediate (Ai) and large (Al). In histograms prepared from seven cases of amyotrophic lateral sclerosis (ALS), the Cl and Al peaks were decreased selectively and severely. This provides evidence for alpha, but not gamma, motor neuron vulnerability. The Cl peak of spinal ganglion neurons and the Al peak of dorsal roots were significantly reduced in number, without a concomitant increase in Ci, Cs, and Ai peaks. This, plus earlier reports of abnormal cutaneous sensation thresholds, abnormal rates of fiber degeneration in cutaneous nerves, and dorsal column demyelination, provides evidence that large afferent neurons are affected in ALS, but to a lesser degree than alpha motor neurons.
The effect of donor specific and nonspecific pretransplant blood transfusion on skin allograft survival was studied in a mouse model, using skin donor-recipient combinations that differed at the K and I regions of the H-2 complex. In the first series of experiments, B6AF1 mice were treated with antilymphocyte serum (ALS) and grafted with DBA/2 skin. This donor-recipient combination differs in the K and I regions of the H-2 complex. Recipients were transfused 10 days before grafting with donor-specific DBA/2 blood or blood from various donors which were either completely incompatible at the H-2 complex with DBA/2 or shared various H-2 specificities with DBA/2. Only donor-specific DBA/2 blood or blood from donors sharing the K and I regions of the H-2 with DBA/2 prolonged DBA/2 skin graft survival. Donor-specific blood was effective over a wide interval between transfusion and grafting (days -50 to -10). In a second series of experiments using congenic strains of mice, the effect of pretransplant transfusions was studied in the B10.D2 to B10.A combination. These strains differ at the K and I region of the H-2, but share the same minor histocompatibility antigens. ALS-treated B10.A recipients were transfused either with donor-specific B10.D2 blood or blood from B10.BR which shares the minor histocompatibility antigens with B10.D2, but differs in the major antigens or DBA/2 blood which shares the majority histocompatibility antigens with B10.D2, but differs in the minor antigens. Only donor-specific blood or blood from the DBA/2 donor sharing the major antigens with the skin donor prolonged graft survival.
Evidence for the presence of suppressor cells in B6AF1 mice bearing long-term C3H skin grafts after multiple blood transfusions and antilymphocyte serum (ALS) treatment is described. Transfer of spleen cells from these mice into secondary B6AF1 recipients given ALS and C3H skin grafts resulted in marked prolongation of graft survival. The spleen cells were also capable of specifically inhibiting the proliferative response of normal B6AF1 responders to C3H stimulator cells in coculture mixed lymphocyte culture (MLC) experiments.