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Biomedical subjects

A J Johnson

Publications and source records attributed to A J Johnson.

At least 109 records · Page 6Linked to original sources

The absorption and elimination of ICI 74,917 in man.

1 The pharmacokinetics of ICI 74,917 were studied in both asthmatic patients and normal volunteers. 2 The tritiated compound was administered to the lungs by inhalation from an aerosol and a bronchoscope, and by intravenous, oral and buccal routes. Radioactivity was measured in plasma, urine, faeces, sputum and exhaled air. 3 After bronchoscopic administration 63% of the available dose was absorbed; after aerosol administration 8% was absorbed from the lung and more than 50% swallowed. 5 Intravenous studies indicated that the drug is excreted in the bile and urine in the ratio 2:1. 5 Minimal oral and no buccal absorption occurred. 6 There was no evidence of tritium exchange or drug metabolism. 7 The mean terminal half-life following administration by all route was 16.1 hours. However, the majority of the dose was rapidly excreted. 8 Aerosol administration is the method of choice for the clinical use of ICI 74,917.

Absorption↗

Metabolic response to intravenous salbutamol therapy in acute asthma.

In patients suffering from an acute attack of asthma the effects of salbutamol infusion (10 microng/min) on their plasma concentrations of non-esterified fatty acids (NEFA), triglyceride, insulin, and glucose were compared with those in a group of asthmatics not requiring infusion. Salbutamol was found significantly to increase the plasma concentrations of glucose and insulin while having little effect on NEFA or triglyceride. However, NEFA concentrations were found to be significantly increased in patients with an acute attack of asthma at the time of their admission to hospital. This increase is attributed to the stress of the asthmatic attack itself.

Acute Disease↗

Detection of hepatitis B surface antigen in potentially contaminated human plasma and plasma fractions.

A new method is described for the quantitative detection of HBsAg in whole human plasma and in plasma fractions. The nonantigen proteins are digested with pepsin at low pH, and the antigen is precipitated with PEG. With use of only 20 ml of contaminated plasma, as few as 5.0 x 10(6) HBsAg particles/ml can be detected--a 40-fold increase in the apparent level of sensitivity of the Ausria II RIA (2.0 x 10(8) particles/ml). With 500 500 ml or more of plasma or plasma fractions, fewer than 5.0 x 10(5) particles/ml can be assayed--a 400-fold increase in RIA sensitivity and 1/10 the antigen concentration found in sera that proved infective when injected into chimpanzees. The pepsin-PEG method was used to quantitate the particles per milliliter in four equivocal RIA samples from the NIH Bureau of Biologics, three of which were definitely shown to contain antigen. The method has also been employed to detect fewer than 2.0 x 1010(8) particles/ml of HBsAg in deliberately contaminated high purity AHF concentrates and may be useful for monitoring plasma fractions prepared on a large scale or for detecting the antigen in equivocal samples from blood banks.

Blood Donors↗

Sheep experimentally infected with sarcocystis from dogs. I. Disease in young lambs.

Eight Polled Dorset lambs were orally inoculated with Sarcocystis ovicanis sporocysts. Two lambs that received 100,000 or 200,000 sporocysts became clinically ill, recovered, and were killed 67 and 88 days after inoculation (DAI). Numerous intramuscular cysts were found in their skeletal and cardiac muscles. Three lambs received 100,000 sporocysts, three lambs received 1 million sporocysts, and three lambs received no sporocysts. After an acute clinical illness characterized by anemia, inappetence, weight loss, fever, and reduced serum protein, all lambs that received 100,000 sporocysts died 27 to 29 DAI and all that received 1 million sporocysts died 24 or 25 DAI. Hemorrhage involving the striated muscle and visceral organs was the most apparent gross lesion. The heart appeared most severely affected. Schizonts were found in vascular endothelial cells of all six inoculated lambs. Uninoculated lambs remained healthy, and neither lesions nor parasites were found in any tissues. Dogs fed tissues containing S. ovicanis cysts produced sporocytes 11 to 37 days after feeding; cats fed similar stages produced no sporocysts. Dogs fed tissues containing schizonts produced no sporocysts.

Animals↗

Purification and characterization of two forms of urokinase.

Affinity chromatography on agmatine-Sepharose was used for the separation of two active forms of urokinase (EC 3.4.99.26) from partially purified human urinary urokinase. The approximate molecular weight of the heavier form was 47 000 and of the lighter 33 400. Both forms were homogeneous by sodium dodecyl sulfate gel electrophoresis and by 3H-labeled diisopropylphosphorofluoridate and 14C-labeled p-nitrophenyl-p'-guanidinobenzoate incorporation studies. The 33 400 mol. wt. form had a single chain, and the 47 000 mol. wt. form had two chains (33 100 and 18 600 mol. wt.) linked by disulfide bonds. The specific activity of the heavier form was 104 000 CTA units/mg protein, compared with 226 000 units/mg for the lighter form but the activities per mmol of active site (molar activities) of the two forms were almost identical (9.6-10(9) and 10.2-10(9) CTA units/mmol). Isoelectric focusing on gels showed that the 47 000 material contained one major subform with a pI of 8.60 and a minor subform with a pI of 8.90, while the 33 400 material had three major subforms with pI values of 8.35, 8.60 and 8.70, respectively, and a minor subform with a pI of 8.05. 3H-labeled diisopropylphosphorofluoridate incorporation studies revealed an active-site serine residue in the heavy chain.

Amino Acids↗

Identification of an active site histidine in urokinase.

Two forms of urokinase (EC 3.4.99.26) with apparent molecular weights of 33 400 and 47 000 purified by affinity chromatography have been modified specifically with newly synthesized peptide chloroketones by affinity labeline. Rapid inactivation of the enzyme preparations was observed with Ac-Gly-Lys-CH2 Cl and Nle-Gly-Lys-CH2 Cl which might be associated with a change in which a histidine residue is lost. After performic acid oxidation, an equivalent amount of 3-carboxymethyl histidine could be recovered, indicating alkylation at the N-3 of a histidine residue. In the case of the norleucine derivative, norleucine was concomitantly incorporated into the protein. It is thus likely that urokinase belongs in the class of enzymes utilizing the Asp..His..Ser triad for their catalytic action. The two active site residues so far identified, serine and histidine, were located in the heavy chain (33 100 mol. wt) of the 47 000 molecular weight form and in the 33 400 molecular weight form, the molecular weight of which remained constant.

Affinity Labels↗

Abortion and other signs of disease in cows experimentally infected with Sarcocystis fusiformis from dogs.

Six five- to eight-year-old multiparous cows were given oral inoculations of sporocysts of Sarcocystis fusiformis five to six and one-half months after field breeding. All cows became ill. Clinical signs of infection included muscle tremors, hypersalivation, reduced consumption of feed, weight loss, excessive shedding of hair, elevated temperature, reduced packed cell volumes and total red blood cell counts, and abortion. One cow aborted on day 41 after inoculation, and another aborted on day 69. A moribund cow was sacrificed, and a normal fetus was found in utero. Two cows did not produce calves; in one of these cows, a fetal skeleton was found in utero at postmortem examination. One cow produced a normal healthy calf. No evidence of congenital transmission of S. fusiformis was found in histologic specimens from the fetuses or the calf. No illness or abortion was observed in any of the 25 uninoculated control cows. This paper is the first report of bovine abortion associated with experimentally induced sarcocystosis.

Abortion, Veterinary↗

Oral infection of mammals with Sarcocystis fusiformis bradyzoites from cattle and sporocysts from dogs and coyotes.

Individual sporocysts containing 4 sporozoites were shed in the feces of dogs, foxes, and raccoons after ingestion of bovine tissue infected with Sarcocystis fusiformis bradyzoites. No sporocysts were shed by cats, monkeys, swine, skunks, ferrets, rats, guinea pigs, or rabbits after ingestion of similar bovine tissue. The shedding of sporocysts by dogs that had ingested tissue from a bovine experimentally infected with sporocysts from coyotes indicated that both canids were definitive hosts for the same species of Sarcocystis. After oral inoculation wtih sporocysts from dogs previously fed infected bovine heart, a calf became infected; but sheep, swine, rats, mice, rabbits, and monkeys did not. These results show the narrow specificity of the asexual stages of this parasite for the bovine intermediate host and the wider, though still restricted, host range of the sexual stages of this parasite for coyotes, dogs, foxes, and raccoons, the definitive hosts.

Animals↗

Removal of hepatitis B surface antigen (HBsAg) from plasma fractions.

Endogenous or deliberately added hepatitis B antigen was removed and concentrated for assay from albumin, and from coagulation factor II, VII, IX, and X concentrates as model plasma fractions. The concentrates carry considerable risk of causing hepatitis in transfused patients. The amount of antigen remaining in the fraction was estimated to be less than 1/10,000 of that detectable by the Ausria II radioimmunoassay and 1/100 of that found to be infectious when highly contaminated human sera were diluted and injected in chimpanzees. Batch fractionation methods with polyethylene glycol were used. The yield of albumin was 96 per cent and of the coagulation factors about 90 per cent.

Blood Proteins↗

Sarcocystis fusiformis infection in the coyote (Canis latrans).

Of 150 fecal samples from coyotes from northern Utah and southern Idaho, 21 contained coccidian sporocysts. These were found singly, contained four sporozoites and a granular residuum, and averaged 16.9 x 10.9 mum in size. None of four lambs inoculated with these sporocysts showed clinical signs of disease, and no parasites were found in their tissues. One calf inoculated with 135,000 sporocysts and another inoculated with 720,000 sporocysts eventually became unable to rise from recumbency. One was killed after 43 days; the other died at 50 days. Both calves had a mild mononuclear cell infiltration into the connective tissue adjacent to vessels in the heart, other striated muscles, kidney, and liver, and a moderate lymphoid hyperplasia in the spleen and lymph nodes. Schizonts were observed in a lymph node, and young sarcocysts were observed in skeletal and cardiac muscles. Four coyotes fed bovine heart infected with Sarcocystis passed sporulated sporocysts in their feces that were indistinguishable from those in the fecal samples from Utah and Idaho.

Animals↗

Effect of intravenous injection of salbutamol in asthma.

The effect of i.v. salbutamol was compared with aerosol salbutamol in ten asthmatic patients. 2 A cumulative dose of salbutamol (300 mug) given in three separate injections over 45 min resulted in a mean increase in peak expiratory flow rate (PEFR) of 38.3% and FEV1 of 36%. 3 There was no significant difference in degree of bronchodilatation to the same dose of salbutamol administered intravenously or by aerosol. 4 Palpitations, tremor, and postural hypotension were common when the drug was injected intravenously over one minute, but did not occur after aerosol administration. 5 It is suggested that sulbutamol by intravenous injection is a useful addition to the treatment of acute asthma.

Adult↗