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Biomedical subjects

R A Hall

Publications and source records attributed to R A Hall.

At least 109 records · Page 6Linked to original sources

Isolation and characterization of dengue viruses serotype 1 from an epidemic in northern Queensland, Australia.

Thirteen strains of dengue type 1 were isolated from the lymphocyte fractions of 69 acute phase blood samples collected at Thursday Island Hospital during 1981 and 1982. One further strain of type 1 was isolated from 7 blood samples despatched by air from Cairns Base Hospital during 1982. Four of these Australian isolates representing the beginning, middle, and end of the epidemic were examined by restriction enzyme mapping and were found to be identical for the nine restriction enzymes used. The maps differed from those derived from two Malaysian dengue type 1 strains isolated during the epidemic of 1981-82 in that country. This suggests reliance on serological typing to establish global circulation patterns of epidemic dengue is insufficient and that more specific methods such as genome mapping are useful.

Adolescent↗

Type-specific monoclonal antibodies produced to proteins of Murray Valley encephalitis virus.

Two monoclonal antibodies have been produced to the flavivirus, Murray Valley encephalitis (MVE). Immunofluorescent antibody and ELISA tests revealed that one antibody was specific for MVE while the other cross-reacted weakly with Alfuy and Kunjin viruses. These antibodies have neither haemagglutination inhibition nor neutralising activity. One of the monoclonal antibodies reacted with the envelope glycoprotein (E) and a 45,000 MW protein, while the other reacted with a protein of 23,000 daltons. Competitive binding assays confirmed that these antibodies reacted with unrelated epitopes.

Antibodies, Monoclonal↗

Pharmacology of L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpro pan oic acid); a potent, selective thromboxane/prostaglandin endoperoxide antagonist.

L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpropa noic acid) has been studied in vitro on the guinea-pig tracheal chain, pulmonary artery and thoracic aorta ring and shown to be a potent, competitive antagonist of contractions induced by the prostaglandin endoperoxide analogue, U-44069 (pA2 values 8.0, 8.4 and 8.0 respectively). Selectivity on the guinea-pig trachea was indicated by non-competitive antagonism of contractions induced by prostaglandin D2 and minimal activity against contractions induced by leukotriene D4, prostaglandin F2 alpha, serotonin, histamine and acetylcholine. L-655,240 was a potent inhibitor of the aggregation of washed human platelets induced by U-44069 (IC50 value 7 X 10(-9) M) and inhibited aggregation of human platelet rich plasma induced by U-44069, U-46619, thromboxane A2 and collagen but not ADP or platelet activating factor. In vivo i.v. L-655,240 administered to guinea-pigs inhibited bronchoconstriction induced by i.v. U-44069 and arachidonic acid (ED50 values 0.09 and 0.23 mg kg-1) but not histamine, acetylcholine or serotonin. When administered to rhesus monkeys (3 and 10 mg/kg p.o.), L-655,240 inhibited ex vivo platelet aggregation induced by U-44069 but not ADP. It is concluded that L-655,240 is a potent, selective, orally active thromboxane/prostaglandin endoperoxide antagonist.

Animals↗

An enzyme immunoassay to detect Australian flaviviruses and identify the encephalitic subgroup using monoclonal antibodies.

An antigen-capture enzyme-linked immunosorbent assay (ELISA) has been developed to detect antigens of Australian flaviviruses in mosquito pools, suckling mouse brain and infected cell culture supernatant fluid. A monoclonal antibody reactive to an epitope on the envelope glycoprotein common to all flaviviruses was used as the capture antibody. Purified rabbit IgG, produced against Murray Valley encephalitis (MVE) virus, which reacted with eight Australian flaviviruses in haemagglutination inhibition (HI) and in an indirect fluorescent antibody test, was used as the indicator antibody in direct and indirect antigen-capture ELISA. A monoclonal antibody specific for a subgroup of encephalitic flaviviruses was conjugated to horseradish peroxidase and used as the indicator antibody to distinguish MVE, Kunjin and Alfuy viruses from the remainder tested. This ELISA could detect viral antigen in mosquito cell culture fluids and suckling mouse brain preparations at titres as low as 1000 TCID50/100 microliters. Viral antigen in a single mosquito infected with MVE could be detected in a pool of 500.

Animals↗

The experimental infection of horses with Murray Valley encephalitis and Ross River viruses.

Eleven weanling horses were inoculated with Murray Valley encephalitis and Ross River viruses either by intravenous injection or by the bite of Culex annulirostris or Aedes vigilax mosquitoes infected orally. Five of the 11 horses circulated trace amounts of MVE virus for 1 to 5d and they infected 7/408 Cx annulirostris which subsequently fed on them. Haemagglutination-inhibiting antibody persisted at detectable levels for the 24-week observation period. With Ross River virus, only one of 11 horses inoculated developed a viraemia detectable by inoculation of suckling mice but 5 horses contained virus sufficient to infect 41/383 Cx annulirostris that fed on them 3 to 4 days after inoculation. On primary inoculation with Ross River virus, only 2 horses developed HI antibody but late responses occurred in 3 horses following probable naturally acquired re-infections. With both viruses, most horses remained normal, some developed mild pyrexia and transient clinical signs. This paper, therefore, indicates that horses are unlikely to be efficient amplifiers of either MVE or RR viruses and does little to incriminate them as important pathogens.

Aedes↗

L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide): a novel thromboxane-prostaglandin endoperoxide antagonist.

The effects of L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide) have been studied on pulmonary and other smooth muscle preparations in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-641,933 produced significant shifts in the dose-response curves to the prostaglandin endoperoxide analogues, U-44069 (pA2 7.06) and U-46619 (pA2 7.14), and prostaglandin (PG) F2 alpha (pA2 6.33) had minimal activity against contractions induced by histamine (pA2 4.38), 5-hydroxytryptamine (pA2 4.63), and acetylcholine (pA2 4.56) and slightly enhanced relaxation induced by PGE2. When tested on the guinea-pig gall bladder strip in vitro, L-641,953 antagonized contractions induced by U-44069 (pA2 7.03) but was less active against those induced by PGF2 alpha (pA2 6.03), PGE1 (pA2 5.62), and histamine (pA2 4.84). When tested in vitro on the guinea-pig pulmonary artery, L-651-953 significantly antagonized contractions induced by U-44069 (pA2 7.04), U-46619 (pA2 7.14), and PGF2 alpha (pA2 7.16) but was less effective against contractions induced by histamine (pA2 4.19). Schild analysis indicated that L-641,953 was fully competitive against contractions of either the guinea-pig tracheal chain induced by U-46619 or the guinea-pig pulmonary artery induced by U-44069 and U-46619. When tested on human platelets in vitro L-641,953 inhibited aggregation induced by U-44069 (IC50 1.3 X 10(-6) M) but not ADP.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Conflict between classifications based on free thyroxine and thyroid stimulating hormone concentrations in thyroxine-treated patients.

The use of free thyroxine assay as the basis for monitoring patients on thyroxine replacement therapy was assessed. Patients with normal free thyroxine levels were divided into sub-groups on the basis of serum TSH levels. Of these, patients with normal TSH levels had higher serum free thyroxine and free 3,5,3'-triiodothyronine concentrations than patients with elevated TSH levels. No significant differences were seen in the level of duration of replacement therapy. Patients were almost equally divided between the high and normal TSH sub-groups. It was concluded that free thyroxine assay had little role to play in the monitoring of these patients.

Humans↗

Experimental infection with Murray Valley encephalitis virus. Pigs, cattle, sheep, dogs, rabbits, macropods and chickens.

A total of 142 young animals including 10 domestic and 14 feral pigs, 12 Hereford calves, 12 crossbred and 24 Merino lambs, 11 dogs, 8 domestic and 16 feral rabbits, 14 Grey kangaroos, 9 Agile wallabies and 12 chickens was exposed to infection with 4 strains of Murray Valley encephalitis virus (MVE), mainly using orally infected Culex annulirostris mosquitoes. In terms of their viraemic response, the animals were grouped into high (Grey kangaroos, rabbits), moderate (pigs, dogs, chickens) and low (calves, lambs, Agile wallabies). Recipient Cx annulirostris induced to bite these animals 1-7 d post-inoculation exhibited infection rates up to 95% but usually were much lower. Some animals in which virus was not detected by intracerebral inoculation of suckling mice were capable of infecting up to 5% Cx annulirostris. Haemagglutination-inhibiting antibody (HI) was of high titre and persistent in rabbits and Grey kangaroos but moderated in others, e.g., cattle, sheep, Agile wallabies to be transient and of low titre. Cattle and Merino lambs were often completely non-responsive. This study increases the range of vertebrates that could be considered as maintenance or amplifying hosts of MVE and, on the basis of their HI antibody responses, evaluates them as potential sentinels of infection in Australia.

Animals↗

Experimental infection with Murray Valley encephalitis virus: galahs, sulphur-crested cockatoos, corellas, black ducks and wild mice.

Orally infected Culex annulirostris or intravenous injections were used to infect 10 Galahs, 15 Sulphur-crested cockatoos, 12 Corellas, 4 Black ducks and 10 wild mice with Murray Valley encephalitis (MVE) virus. The birds produced moderate viraemias of titres of log 10(2.0)-10(6.0) suckling mouse intracerebral (SMIC) LD50/ml for durations of 1-9 d. However, the wild mice developed low grade viraemia for 1-4 d. Recipient Cx annulirostris feeding on viraemic birds sustained infection rates of 0-10% but, by extrapolation from vector competence data, some titres were capable of infecting greater than or equal to 50% of recipient Cx annulirostris. HI antibody responses were moderately high for most birds (reciprocal titres of 1 in 640-2560) by 14 d and usually persisted at detectable levels for 140 d and, in some individuals, for 6 months. However, 6 of 12 Corellas and 1 of 4 Black ducks became seronegative after 42 and 56 d, respectively. As with previously tested animals, any IgM response was absent 4 wks post-infection. The viraemias attained indicate that these bird species may be considered as potential hosts of MVE, but the limited viraemic response of wild mice suggests that they might play only a minor role.

Animals↗

R-enantiomer of timolol: a potential selective ocular antihypertensive agent.

Various studies were conducted to evaluate the effects of timolol, an S-enantiomer, relative to its R-enantiomer upon intraocular pressure and related ocular systems in the rabbit. The R-enantiomer was about one-third as potent as timolol in displacing 3H-dihydroalprenolol binding to iris-ciliary body tissue, reducing aqueous humor formation, and lowering intraocular pressure of alpha-chymotrypsin hypertensive eyes. In contrast, the R-enantiomer was 50 to 90 times less potent than timolol in antagonizing the effects of isoproterenol on pulmonary and atrial beta-adrenergic receptors. The data indicate that the R-enantiomer may lower intraocular pressure in man at concentrations less likely than timolol to block extraocular beta-adrenergic receptors. Finally, to account for the differential effect of the R-enantiomer upon ocular as opposed to extraocular beta-adrenergic receptors, it is tentatively suggested that this agent may also act upon a population of ocular beta-adrenergic receptors showing relatively poor stereoselectively.

Animals↗

Effects of a contractile prostaglandin antagonist (L-640,035) upon allergen-induced bronchoconstriction in hyperreactive rats and conscious squirrel monkeys.

The effects of an antagonist of contractile prostanoids, L-640,035 (3-hydroxymethyl-dibenzo[b,f]thiepin-5-dioxide) upon antigen-induced bronchoconstriction have been studied in inbred rats with non-specific bronchial hyperreactivity and in conscious squirrel monkeys. L-640,035 was a potent inhibitor of antigen-induced dyspnea (ED50 3.1 mg/kg p.o.) in inbred rats pretreated with methysergide (3 micrograms/kg i.v.) but produced no significant inhibition in untreated rats. Administration of L-640,035 (10 mg/kg p.o.) to conscious squirrel monkeys exposed to aerosols of ascaris antigen markedly inhibited changes in pulmonary resistance (RL) and dynamic compliance (CDYN). At a lower dose (1 mg/kg p.o.) the inhibition of changes in CDYN were similar but the effects on RL were reduced. It was concluded first that contractile prostanoids may be important mediators of antigen-induced bronchoconstriction and secondly that L-640,035 may be effective in human allergic asthma.

Airway Resistance↗

Studies on L-640,035: a novel antagonist of contractile prostanoids in the lung.

The effects of L-640,035 (3-hydroxymethyl-dibenzo [b,f] thiepin-5,5-dioxide) have been studied on pulmonary smooth muscle contraction in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-640,035 produced significant shifts in the dose-response curves to a prostaglandin (PG) endoperoxide analogue (U-44069) (pA2 7.0), PGF2 alpha (pA2 5.9) and PGD2 (pA2 6.5). L-640,035 produced no significant shift in the dose-response curves to leukotriene D4 or histamine and produced a small but statistically significant shift in the dose-response curve to 5-hydroxytryptamine (5-HT) (pA2 5.2). With the exception of PGF2 alpha, Schild analysis did not in general indicate competitive inhibition. The main metabolite of L-640,035, L-636,499, also produced significant parallel shifts in the dose-response curves to U-44069 (pA2 6.0) and PGF2 alpha (pA2 6.0), but with some reduction in the maximal contraction. When L-640,035 was administered intravenously to guinea-pigs, significant inhibition of increases in pulmonary resistance or insufflation pressure induced by U-44069 (ED50 0.16 mg kg-1), leukotriene D4 (ED50 0.25 mg kg-1) and 5-HT (ED50 3.4 mg kg-1) but not histamine (ED50 greater than 10 mg kg-1) was observed. When L-640,035 was administered intravenously to dogs a significant inhibition of increases in pulmonary resistance induced by U-44069 (ED50 0.85 mg kg-1) but not histamine (ED50 greater than 30 mg kg-1) was observed. 5 When L-640,035 was administered by the intraduodenal route to dogs at doses of 3 and 10 mg kg- significant inhibition of increases in pulmonary resistance induced by sodium arachidonate (3 mgkg1 i.v.) was observed with a duration of action of > 255 min. 6 It is concluded that L-640,035 is a novel, relatively selective, and orally active antagonist of the actions of contractile prostanoids on pulmonary smooth muscle.

Airway Resistance↗

Inhibition of prostanoid-mediated platelet aggregation in vivo and in vitro by 3-hydroxymethyl-dibenzo(b,f)thiepin 5,5-dioxide (L-640,035).

Platelet aggregation was studied in vitro with human platelets and in vivo in guinea pigs and rabbits. L-640,035 and its acetic acid metabolite, L-636,499, significantly inhibited human platelet aggregation induced by arachidonic acid, collagen and a prostaglandin endoperoxide analog (U44069) but not ADP. In guinea pigs, circulating platelets labeled with 111indium were monitored with probes in the lung and abdominal regions. Platelet aggregation was indicated by an increase in the ratio of gamma-radiation of the lung vs. the abdominal region, as aggregates of platelets accumulate in the microvascular network in the lung. L-640,035 (1 and 3 mg/kg i.v.) inhibited platelet aggregation induced in this model by U-44069 but not by ADP. In rabbits acute thrombosis was induced in the carotid artery by local electrical stimulation and platelet accumulation at the stimulus site was quantitated using 111indium-labeled autologous platelets. L-640,035 (1 and 3 mg/kg i.v.) significantly reduced electrically evoked platelet accumulation. It is concluded that L-640,035 is a novel and selective antagonist of platelet aggregation induced by thromboxane A2 or prostaglandin endoperoxides and that it may have utility as an antiplatelet drug.

Adenosine Diphosphate↗

Contraction of guinea pig gall bladder strips by leukotrienes and other agonists.

In the presence of indomethacin, Leukotriene C4 (LTC4), LTD4 and LTE4 were shown to be contractile agents in vitro on guinea pig gall bladder strips. The respective pD2 values for LTC4, LTD4 and LTE4 were 9.1, 9.1 and 7.7. The contractile effects of LTD4 were not mediated through the generation of cyclooxygenase products and were antagonized by the SRS-A antagonist FPL-55712. The effects of PGE1, PGF2 alpha, the endoperoxide analogue U44069 and histamine on gall bladder strips were also examined. All these agents caused dose-related contractions but were considerably less potent than the leukotrienes. Leukotrienes are therefore potent contractile agents on the guinea pig gall bladder and may contribute to gall bladder contractions or spasms in vivo.

Alprostadil↗

Thyroxine binding globulin (TBG) and thyroxine binding prealbumin (TBPA) measurement, compared with the conventional T3 uptake in the diagnosis of thyroid disease.

An electroimmunoassay for the determination of thyroxine binding prealbumin is described. The diagnostic efficiency of the assay when used in conjunction with the serum thyroxine as a thyroxine: thyroxine binding prealbumin ratio, is compared with the conventional free thyroxine index and the more recently developed thyroxine: thyroxine binding globulin ratio. The population studied included euthyroid, hypothyroid and hyperthyroid patients and also those who were either pregnant or receiving oral contraceptive therapy. Despite recent evidence establishing the theoretical/practical advantages of using a direct measurement for thyroid binding proteins rather than an indirect method (tri-iodothyronine uptake), results obtained from this study suggest that, for the majority of patients requiring biochemical assessment, the free thyroxine index is still the superior discriminator of thyroid abnormality.

Female↗