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Biomedical subjects

B Oberg

Publications and source records attributed to B Oberg.

At least 127 records · Page 7Linked to original sources
PubMed1983

9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication.

A new compound, 9-(3,4-dihydroxybutyl)guanine, has been synthesized and its antiherpes activity determined. 9-(3,4-Dihydroxybutyl)guanine was selectively phosphorylated by herpes simplex virus thymidine kinase and had a high affinity for this enzyme, with an inhibition constant of 1.5 microM. In cell culture, replication of different strains of herpes simplex virus types 1 and 2 was inhibited to the extent of 50% by 4 to 18 microM (RS)-9-(3,4-dihydroxybutyl)guanine. The (R)-enantiomer of this compound was more inhibitory than the (S)-enantiomer. Herpesvirus DNA synthesis was selectively inhibited by (RS)-9-(3,4-dihydroxybutyl)guanine in infected cells, and a low cellular toxicity was observed. (RS)-9-(3,4-Dihydroxybutyl)guanine had a therapeutic effect when applied topically to guinea pigs with cutaneous herpes simplex type 1 infections and to rabbits with herpes keratitis. Oral treatment of a generalized herpes simplex type 2 infection in mice had a therapeutic effect.

Acyclovir↗
PubMed1983

Kinetic analysis in cell culture of the reversal of antiherpes activity of nucleoside analogs by thymidine.

The inhibition of herpes simplex virus type 1 plaque formation by acyclovir, bromovinyldeoxyuridine, 9-(3,4-dihydroxybutyl)guanine, and 9-(4-hydroxybutyl)guanine at different thymidine concentrations was analyzed in Lineweaver-Burk plots. Linear competitive patterns between thymidine and the nucleoside analogs were observed for the inhibition of herpes simplex virus type 1 plaque formation. A new constant, the reversal constant Kr, was introduced to describe the sensitivity in cell culture of an antiviral drug to the reversal of its viral activity by a metabolite (e.g., thymidine).

Animals↗
PubMed1982

Precipitation of nucleotides by calcium phosphate.

Earlier it has been shown that nucleic acids of high molecular weight can be be introduced into cells by coprecipitation with calcium phosphate. We have studied the requirements for calcium phosphate coprecipitation of shorter nucleotides. The degree of coprecipitation of dodecanucleotides lacking terminal phosphate varied between 25 and 72%. Tetramers with a 5'-monophosphate were coprecipitated to 29-87% by calcium phosphate. A high content of guanosine residues and an increased number of terminal phosphate groups increased the degree of coprecipitation of nucleotides. The trinucleotide pppA2'p5'A2'p5'A was effectively precipitated by calcium phosphate but the monophosphate and the core structure were not.

Calcium Phosphates↗
PubMed1982

Pyrophosphate analogues as inhibitors of DNA polymerases of cytomegalovirus, herpes simplex virus and cellular origin.

Several pyrophosphate analogues have been compared for their ability to inhibit the activities of isolated cytomegalovirus (CMV) DNA polymerase, herpes simplex virus type 1 (HSV 1) DNA polymerase and calf thymus DNA polymerase alpha. The most effective inhibitors were phosphonoformate and phosphonoacetate. Although not identical, the structural requirements for compounds inhibitory to CMV and HSV-1 DNA polymerase were specific, with two negatively charged groups in close vicinity. The CMV DNA polymerase was more susceptible to certain phosphonoacetates containing bulky hydrophobic alpha-substituents than was the HSV-1 DNA polymerase. No example of the converse preference was found. The inhibition of CMV DNA polymerase by phosphonoformate, hypophosphate, alpha-hydroxyphosphonoacetate and alpha-nonylphosphonoacetate was linear non-competitive with the deoxyribonucleoside triphosphates as variable substrates. Phosphonoformate, phosphonoacetate, and to a lesser extent alpha-hydroxyphosphonoacetate, carbonyldiphosphonate and alpha-nonylphosphonoacetate also inhibited the focus formation by CMV in cell-culture.

Animals↗
PubMed1982

Inhibition of reverse transcriptase activity of avian myeloblastosis virus by pyrophosphate analogues.

Several pyrophosphate analogues have been studied for their effects on avian myeloblastosis virus reverse transcriptase and on cellular DNA polymerase alpha. Examination of structure-activity relationships for these compounds revealed that two acidic groups connected by a short bridge were necessary, but not sufficient, for inhibition of the enzyme activities. Foscarnet sodium (trisodium phosphonoformate) was the most potent inhibitor of reverse transcriptase, giving non-competitive inhibition of reactions primed by (rA)n . (dT)12-18, (rC)n . (dG)12-18, (dC)n . (dG)12-18, and activated DNA. Carbonyldiphosphonate and 2-hydroxyphosphonoacetate also caused non-competitive inhibition patterns, whereas hypophosphate and imidodiphosphonate inhibited AMV reverse transcriptase in a competitive, non-linear manner. The reverse transcriptase reactions directed by (rA)n . (dT)12-18 and activated DNA were most affected by the non-competitive inhibitors. Hypophosphate and imidodiphosphonate inhibited preferentially reactions primed by (dC)n . (dG)12-18 and activated DNA. In all cases the (rC)n . (dG)12-18 directed reaction was the least affected.

Avian Leukosis Virus↗
PubMed1982

Therapeutic effects of foscarnet sodium and acyclovir on cutaneous infections due to herpes simplex virus type 1 in guinea pigs.

The therapeutic effects of topically applied foscarnet sodium and acyclovir on cutaneous infections due to herpes simplex virus type 1 (HSV-1) were studied in guinea pigs. Foscarnet cream (3%) reduced both the cumulative vesicle score and the time for healing when HSV-1 strains C42 and 79 were tested. The application of foscarnet in cream form resulted in a dose-dependent reduction in skin virus titers and vesicle scores at concentrations ranging from 0.05% to 3%. Infections due to HSV-1 strain 79, but not those due to strain C42, were sensitive to treatment with 5% acyclovir in polyethylene glycol ointment. Topical application of 3% acyclovir in dimethyl sulfoxide on infections due to HSV-1 strain C42 resulted in a reduction in the skin virus titers, lesion scores, and the time for healing. Acyclovir, in both polyethylene glycol and dimethyl sulfoxide, was consistently less active than foscarnet cream in these animal experiments.

Acyclovir↗
PubMed1982

No in vivo effect of trisodium phosphonoformate on woodchuck hepatitis virus production.

The efficient in vitro inhibition of hepatitis B virus DNA polymerase by trisodium phosphonoformate (PFA, INN: foscarnet sodium) and its low toxicity suggested that PFA could be used as a therapeutic agent for hepatitis B infection. PFA was also found to inhibit woodchuck hepatitis virus (WHV) DNA polymerase in vitro. As a model to test PFA's eventual effect, chronically WHV infected woodchucks were treated with PFA. The animals were treated twice daily in a dosage which gave a minimum serum level of PFA corresponding to an in vitro inhibiting effect on WHV DNA polymerase of about 40%. The concentration in liver tissue was found to be 15% below serum level. The amount of WHV particles in serum was followed by DNA polymerase assay. No effect on WHV production could be seen during 2 weeks' treatment. No change of the in vitro sensitivity to PFA of the WHV DNA polymerase was seen. These results indicate that the WHV associated DNA polymerase has no role in the production of viral particles.

Animals↗
PubMed1982

Lower extremity goniometric measurements: a study to determine their reliability.

Two series of healthy men were measured for range of passive motion of hip flexion, hip extension, hip abduction, knee flexion, and ankle dorsiflexion with the knee extended and flexed. Hip abduction was measured with a specially constructed double protractor goniometer, and the other movements were gauged with a flexometer. In series A measurements were based upon a commonly used clinical method. The intratester interassay coefficient of variation in series A was 7.5 +/- 2.9%, which corresponded well with other reports. In series B posture and measuring procedures were rigidly standardized by better fixation and by identification and marking of anatomical landmarks. The interassay coefficient of variation in series B was reduced to 1.9 +/- 0.7%. Range of motion measurement was repeated accurately by the same tester with methods requiring careful measurement technique but no elaborate equipment.

Ankle Joint↗
PubMed1981

Inhibitory effects of foscarnet on herpesvirus multiplication in cell culture.

The effect of phosphonoformate (INN; foscarnet sodium) on Herpes Simplex Virus type 1 replication in cell-culture has been studied. At 55 microM, foscarnet reduced the yield by 50 per cent which correlated well with a 50 per cent reduction of plaque formation at 60 microM. Foscarnet had to be added before 8 hours post infection to inhibit virus production. The inhibition of herpesvirus plaque formation by the presence of foscarnet for 24 hours was not reversed by the removal of the drug. The inhibition of virus replication by foscarnet could, in contrast to the inhibition by acycloguanosine, not be reversed by addition of deoxynucleosides.

Animals↗
PubMed1981

Antiherpes activity of [E]-5-(1-propenyl)-2'-deoxyuridine and 5-(1-propenyl)-1-beta-D-arabinofuranosyluracil.

5-(1-Propenyl)-1-beta-D-arabinofuranosyluracil has been synthesized, and this compound and [E]-5-(-propenyl)-2'-deoxyuridine have been tested for inhibition of herpes virus multiplication. Only [E]-5-(1-propenyl)-2'-deoxyuridine was found to be an active inhibitor reducing by 50% the plaque formation of herpes simplex virus type 1 (HSV-1) at about 1 muM. A comparison to the bromovinyl derivatives showed the following order of descending activity; [E]-5-(2-bromovinyl)-2'-deoxyuridine greater than 5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil greater than or equal to [E]-5-(1-propenyl)-2'-deoxyuridine greater than 5-(1-propenyl)-1-beta-arabinofuranosyluracil. HSV-1 mutants lacking thymidine kinase or resistant against acycloguanosine were resistant against [E]-5-(1-propenyl)-2'-deoxyuridine. All compounds seemed to be phosphorylated by HSV-1 thymidine kinase in a cell-free assay. The compounds were phosphorylated to a lower extent by cellular or HSV-2 thymidine kinase, and the HSV-2 strains tested were inhibited by less than 50% at 100 muM in plaque assays. A selective inhibition of HAV-1 DNA synthesis by [E]-5-(1-propenyl)-2'-deoxyuridine was observed in infected cells indicating an effect on viral DNA polymerase. [E]-5-(1-Propenyl)-2'-deoxyuridine had a low cellular toxicity and a therapeutic effect when applied topically to HSV-1-infected guinea pig skin.

Animals↗
PubMed1981

Functional analysis of influenza RNA polymerase activity by the use of caps, oligonucleotides and polynucleotides.

The effects of caps, dinucleotides, oligonucleotides and polynucleotides on influenza virus RNA polymerase activity have been investigated. The results show that both methyl groups in a cap are necessary for optimal stimulation of polymerase activity. Both m7G(5')ppp(5')Am and ApG stimulated the influenza RNA polymerase activity and seemed to interact at different sites. Out of the 16 homopolynucleotides tested, seven inhibited influenza RNA polymerase by 50% at 2-10 micrograms/ml. Poly(G) gave a 90% reduction of influenza virus plaque formation at 10 micrograms/ml. An oligodeoxyribonucleotide complementary to the 12 terminal nucleotides of the 3' end of influenza virus RNA was synthesized. This oligonucleotide did not selectively inhibit influenza RNA polymerase.

DNA-Directed RNA Polymerases↗
PubMed1981

Studies on the endoanesthetic effects of lidocaine and benzonatate on non-medullated nerve endings in the left ventricle.

The blocking (endoanesthetic) effects of lidocaine (Xylocaine) and benzonatate (Tessalon) on cardiac ventricular, non-medullated endings were tested in cats. Lidocaine was found to cause an effective and long-lasting partial blockade of the cardiovascular reflex responses to stimulation of the ventricular receptors. This effect was obtained at plasma concentrations of 2.5-4.7 microgram/ml, which is within the concentration range seen in patients with myocardial infarction treated with lidocaine because of its antiarrhythmic properties. Tessalon also markedly attenuated the reflex response, normally obtained when the ventricular receptors are excited, but the effect was very shortlasting when doses, producing no side effects, were used. Recordings of impulse traffic from the left ventricular receptors showed that the impaired reflex responses after lidocaine and Tessalon were due to a blockade at the receptor level. Thus both the receptor response to ventricular distension and to injection of protoveratrine (Bezold-Jarisch reflex) was markedly attenuated after infusion of lidocaine (2-4 mg/kg) or a bolus injection of Tessalon (0.2-1 mg/kg).

Animals↗
PubMed1981

Arterial baroreceptor reflex function during elevation on intracranial pressure.

The ability of the arterial baroreceptor reflex to buffer the blood pressure responses elicited by increasing the intracranial pressure (ICP) has been studied in chloralose anesthetized cats. Standardized elevations of ICP induced pressor responses of similar magnitude irrespective of whether the baroreceptor inhibitory activity was high or vey low. When ICP was elevated baroreceptor activation induced a reflex reduction of flow resistance and blood pressure, but never to the same levels obtained when ICP was normal. Thus when ICP was elevated there was an upward displacement of the curve relating carotid sinus pressure to mean arterial blood pressure.

Animals↗
PubMed1981

Reflex cardiovascular responses to graded stimulations of low- and high-threshold afferents in the carotid sinus and aortic nerves in the cat.

Reflex responses to electrical stimulation of low-threshold and high-threshold afferents in the aortic and carotid sinus nerves were investigated in chloralose-anesthetized cats. Changes in blood pressure, heart rate and muscle resistance were recorded. Low-threshold stimulation induced depressor responses of moderate magnitude. When stimulation intensity was increased to engage also the high threshold aortic nerve afferents a more pronounced reflex response was seen even with stimulation frequencies less than 10 Hz. Furthermore, stimulation of low- and high-threshold aortic nerve afferents induced different reflex patterns. For a given fall in blood pressure, the low-threshold afferents induced a greater reflex decrease in muscle vascular resistance compared with the high-threshold afferents, which reduced heart rate more. The effects seen at low frequency stimulation of high-threshold aortic nerve afferents were interpreted to reflect activation of the non-medullated baroreceptor afferents, while the depressor reflexes at low-threshold stimulation were induced by medullated baroreceptor afferents. Also the reflex effects of continuous and intermittent stimulation patterns of the various afferents were compared. At the same number of imp/s an intermittent stimulation of the low-threshold afferents induced greater reflex changes in blood pressure and muscle vascular resistance but smaller changes in heart rate. No such difference was observed when high-threshold afferents were similarly stimulated.

Animals↗
PubMed1980

Pyrophosphate analogues as inhibitors of herpes simplex virus type 1 DNA polymerase.

Twenty nine pyrophosphate analogues have been tested for their ability to inhibit herpes simplex virus type 1 (HSV-1) DNA polymerase activity. The structural requirements for active inhibitors and their mechanism of action have been investigated. Active compounds had two negatively charged groups at close proximity. The most active compounds contained free phosphono and/or carboxyl groups. Apart from phosphonoformate and phosphonoacetate, which were strong inhibitors, some other analogues, 2-phosphonopropionate, 2-phenylphosphonoacetate, oxalate, carbonyldiphosphate, methanehydroxy-diphosphonate and hypophosphate also inhibited the HSV-1 DNA polymerase activity. With the exception of hypophosphate the tested compounds inhibited the activity of calf thymus DNA polymerase alpha to a lesser extent than the activity of the HSV-1 DNA polymerase. All inhibitors gave linear uncompetitive inhibition of HSV-1 DNA polymerase with activated DNA as variable substrate. With the four deoxynucleoside triphosphates as variable substrates all inhibitors except hypophosphate gave linear non-competitive inhibition patterns. Hypophosphate caused a more competitive type of inhibition. The inhibition constants for the active compounds have been determined. Phosphonoformate, phosphonoacetate, methanehydroxydiphosphonate and hypophosphate also inhibited HSV-1 plaque formation in cell culture.

Animals↗
PubMed1980

Cardiovascular effects elicited from the ventral surface of medulla oblongata in the cat.

Cardiovascular adjustments induced by topical application of drugs on a restricted area on the ventral surface of the medulla oblongata, corresponding to the caudal part of the rostral chemoreceptor area and the intermediate area, have been studied in chloralose-anesthetized cats. Topical application of GABA or glycine on these structures resulted in blood pressure fall, bradycardia, vasodilatation in the kidney and the skeletal muscles and also depression of respiration. Similar responses except for a slight tachycardia occurred with application of physostigmine. Application of GABA resulted in a marked attenuation of the reflex vasoconstrictor responses to removal of arterial baroreceptor restraint (carotid occlusion), particularly in the kidney, and to disappearance of the reflex renal vasodilatation to baroreceptor stimulation. The findings suggest that GABA application leads to a general diminution of the tonic vasomotor neuron activity, and with regard to renal vasomotor neurons a virtual cessation. Atropine methylnitrate application induced blood pressure rise, increased peripheral resistance in both skeletal muscle and kidney and a strongly potentiated renal vasoconstrictor response to carotid occlusion. The results indicate that the studied superficial medullary structures play an important role for the maintenance of tonic vasomotor neuron activity, especially renal.

Animals↗