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Biomedical subjects

A J Johnson

Publications and source records attributed to A J Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Effect of acute inhibition of lipolysis on operation of the glucose-fatty acid cycle in hepatic cirrhosis.

Hepatic cirrhosis is frequently associated with glucose intolerance and insulin resistance, but the mechanisms underlying the insulin insensitivity are unknown. Plasma concentrations of nonesterified fatty acids (NEFA) are typically elevated in cirrhosis, and the glucose-fatty acid cycle provides a mechanism by which fatty acids may play a role in regulating glucose metabolism. We have therefore investigated the effect of acute inhibition of lipolysis, using the nicotinic acid analogue, acipimox, in 10 male patients with cirrhosis. All subjects were studied in the postabsorptive state after a 10- to 12-hour fast and were given either acipimox 250 mg or a placebo orally 2 hours before a 75-g oral glucose tolerance test (OGTT) and an infusion of insulin (50 mU/kg/h) and glucose (6 mg/kg/min) (insulin sensitivity tests [IST]). The drug was taken in a double-blind crossover design for each test. During the 2 hours following acipimox, there were rapid decreases in plasma NEFA, glycerol, and 3-hydroxybutyrate, confirming inhibition of lipolysis, while there were significant decreases in glucose, insulin, and C-peptide (P less than .001) compared with patients receiving the placebo. Acipimox blunted the increase in glucose after oral glucose loading and decreased incremental glucose concentration (from 579 +/- 76 to 445 +/- 65 mmol/min/L, P less than .02) and incremental insulin concentration (from 13.4 +/- 2.5 to 9.0 +/- 1.4 U/min/L, P = .056) in the OGTT. Improvements in classification of glucose tolerance were seen in five subjects. During the IST, significant reductions occurred in steady-state blood glucose (to 8.8 +/- 1 mmol/L, P less than .02) and C-peptide (to 3.0 +/- 0.5 nmol/L, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

Enhancement of the antibody response to flavivirus B-cell epitopes by using homologous or heterologous T-cell epitopes.

We have been investigating the T-helper (Th)-cell response to the flavivirus envelope (E) glycoprotein. In our studies with Murray Valley encephalitis (MVE) virus, we previously identified synthetic peptides capable of priming Th lymphocytes for an in vitro antivirus proliferative response (J. H. Mathews, J. E. Allan, J. T. Roehrig, J. R. Brubaker, and A. R. Hunt, J. Virol. 65:5141-5148, 1991). We have now characterized in vivo Th-cell priming activity of one of these peptides (MVE 17, amino acids 356 to 376) and an analogous peptide derived from the E-glycoprotein sequence of the dengue (DEN) 2, Jamaica strain (DEN 17, amino acids 352 to 368). This DEN peptide also primed the Th-cell compartment in BALB/c mice, as measured by in vitro proliferation and interleukin production. The failure of some MVE and DEN virus synthetic peptides to elicit an antibody response in BALB/c mice could be overcome if a Th-cell epitope-containing peptide was included in the immunization mixture. A more detailed analysis of the structural interactions between Th-cell and B-cell epitope donor peptides revealed that the peptides must be linked to observe the enhanced antibody response. Blockage or deletion of the free cysteine residue on either peptide abrogated the antibody response. The most efficient T-B-cell epitope interaction occurred when the peptides were colinearly synthesized. These Th-cell-stimulating peptides were also functional with the heterologous B-cell epitope-containing peptides. The Th-cell epitope on DEN 17 was more potent than the Th-cell epitope on MVE 17.

Amino Acid Sequence↗
PubMed1991

Synthetic peptides of the E2 glycoprotein of Venezuelan equine encephalomyelitis virus. II. Antibody to the amino terminus protects animals by limiting viral replication.

A peptide composed of the amino-terminal 25 amino acids of the E2 glycoprotein of the virulent Trinidad donkey (TRD) strain of Venezuelan equine encephalomyelitis virus was found to protect peptide-immunized mice from lethal TRD virus challenge (Hunt et al., 1990). Viral growth in peptide-immunized animals was found to be limited in comparison to that in nonimmunized controls. Although both treated and control groups of mice responded to virus challenge by producing neutralizing antibody, only immunized mice with preexisting antipeptide antibody survived. Polyclonal antipeptide sera as well as a monoclonal antipeptide antibody were able to passively protect naive mice from TRD virus challenge, despite the fact that these antibodies were nonneutralizing. Passive transfer of antipeptide antibody to immunosuppressed recipients was not protective, thus indicating that survival of TRD virus challenge required an in situ immune response as well as preexisting antipeptide antibody. Binding studies of both polyclonal and monoclonal antipeptide antibodies indicated that they recognize only epitopes present on virus-infected cells or denatured virus.

Animals↗
PubMed1990

Pathogenesis of Rift Valley fever in rhesus monkeys: role of interferon response.

Rhesus monkeys inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys had high-titered viremias but disease ranged from clinically inapparent to death. Three (18%) RVF virus-infected monkeys developed signs of hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived RVF viral infection but, 7 showed clinical signs of illness characterized by diminished food intake, cutaneous petechiae, and occasional vomiting. The other 7 monkeys showed no evidence of clinical disease. All monkeys had detectable serum interferon 24-30 h after infection, but 4 of 7 monkeys that did not develop clinical illness had serum interferon titers within 12 h after infection. In lethally infected macaques, indices of hepatic function and blood coagulation were abnormal within 2 days, implicating early pathogenetic events as critical determinants of survival. Serum transferase values were elevated in proportion to severity of clinical disease and outcome of infection. Both myocardial damage and laboratory evidence consistent with disseminated intravascular coagulation were present in fatal infections. All surviving monkeys developed neutralizing antibodies to RVF virus 4-7 days after infection, and this coincided with termination of viremia. Two fatally infected monkeys were viremic until death on days 6 and 8, and the third cleared viremia on day 5 and developed antibody on day 6 but died on day 15. There was a significant correlation between a delayed interferon response and mortality, suggesting that the early appearance of interferon was influential in limiting the severity of disease.

Analysis of Variance↗
PubMed1979

Quantitative N-terminal analysis of fibrinogen-fibrin-related antigen [FR antigen] from human plasma.

Fibrinogen-fibrin-related antigen (FR antigen) was isolated from as little as 1 ml of human plasma by immuno-affinity chromatography with agarose-bound antibody to human fibrinogen. N-terminal analysis was performed to determine the nature and extent of proteolytic degradation of the FR antigen in patients with disseminated intravascular coagulation and in normal subjects. Thrombin cleavage of the A- and B-peptides from fibrinogen in vitro was monitored by the appearance of N-terminal glycine, and an increase in glycine was shown in the FR antigen of patients with disseminated intravascular coagulation. As plasmin progressively degraded fibrinogen, increases in N-terminal alanine, aspartic acid and lysine were observed, corresponding to the known plasmin-cleavage points of fibrinogen; increases in these N-terminal amino acids were also found in the patients' FR antigen. Thrombin treatment in vitro was used to remove fibrinopeptide A (N-terminal alanine) from the samples and to reflect specifically the N-terminal alanine at the plasmin-cleavage point (Arg-42-Ala-43) of the B beta-chain on assay; this alanine was increased progressively in the FR antigen of a patient during urokinase therapy, and was high in other patients when the FR antigen was examined by this procedure.

Alanine↗
PubMed1979

Transmission of Sarcocystis suihominis from humans to swine to nonhuman primates (Pan troglodytes, Macaca mulatta, Macaca irus).

Sporocysts of Sarcocystis suihominis obtained from human feces were used to infect swine. Heart, tongue, and skeletal muscle from experimentally infected and noninfected control swine were fed via stomach tube to nonhuman primates including chimpanzees (Pan troglodytes), rhesus monkeys (Macaca mulatta), and cynomolgus monkeys (Macaca irus). All primates fed infected swine tissues shed sporocysts beginning 13 to 15 days postinfection and were still shedding sporocysts at the conclusion of the experiment, 30 days postinfection. Rhesus and cynomolgus monkeys were fed infected swine tissues a second time and shed sporocysts. All primates remained in good health throughout both experiments and exhibited no unusual clinical signs as a result of infection.

Animals↗
PubMed1979

The gastrointestinal absorption of PRD-92 Ea, a new anti-allergy drug.

1 The absorption of PRD-92 Ea, a new anti-allergy drug, was studied in volunteer subjects. 2 The 14C-labelled drug was administered orally and the radioactivity measured in plasma, urine and faeces. 3 Mean peak plasma concentration was 3.3 micrograms/ml, with a concentration of over 1 micrograms/ml maintained 4 h after administration. 4 The mean plasma half-life (T 1/2) was 114 min. 5 The mean percentage recovery in the urine was 9.5%. 6 Oral administration leads to significant and sustained plasma concentrations, and the oral route should be suitable for drug evaluation in clinical practice.

Adult↗
PubMed1979

Enhanced yield of antihemophilic factor and von Willebrand factor by cryoprecipitation with polyethylene glycol.

A procedure involving cryoprecipitation of human plasma in the presence of polyethylene glycol results in consistently higher yields of antihemophilic factor and von Willebrand factor than were heretofore achieved by cryoprecipitation alone. The resulting AHF and vWF are at least as pure as ordinary cryoprecipitate and can easily be further purified by additional processing. The method is expected to be especially useful in the preparation of AHF and vWF concentrates for the treatment of patients with hemophilia or von Willebrand's disease.

Blood Coagulation Factors↗
PubMed1979

Freedom from transmission of hepatitis-B of gamma-globulin and heat-inactivated plasma protein fraction prepared from contaminated human plasma by fractionation with solid-phase polyelectrolytes.

Plasma contaminated with hepatitis B surface antigen (HBsAg) and shown by others to be infectious when injected in a dilution of 1:1,000,000 in chimpanzees, was fractionated by a solid-phase polyelectrolyte (PE) procedure for its content of plasma protein fraction (PPF) and gamma-globulin (immune serum globulin; ISG). Quantitative Ausria II radioimmunoassays showed that nearly half the HBsAg was bound by the PE and could be eluted at low pH, while the rest was found in the heat-inactivated PPF. When the ISG was concentrated to 16%, the 13 mg/kg (comparable to a human dose) was injected intramuscularly in 6 chimpanzees, or when the PPF was heated at 60 degrees C for h and injected intravenously in 2 chimpanzees, there was no clinical or laboratory evidence of hepatitis B infection after 12 months, although 1 chimp of 2 who received the same material showed a borderline positive anti-HBsAg antibody result on one of 52 weekly serum samples. Since the new PE fractionation method is essentially nondenaturing, and simpler than the classical ethanol procedures, it was important to establish the noninfectivity of the final products.

Adsorption↗
PubMed1978

Purification and properties of porcine platelet aggregating factor.

Porcine platelet aggregating factor was purified from porcine plasma by a rapid batch procedure which included polyethylene glycol precipitation and adsorption on calcium citrate. The aggregating factor was separated from antihemophilic factor by gel chromatography in the presence of 1 M MgCl2. It appeared homogenous when examined by immuno- or SDS-gel electrophoresis. The molecular weight was estimated to be 10 million by exclusion chromatography. After reduction, subunit molecular weight, by sodium dodecyl sulfate (SDS)-gel electrophoresis, was 225 000. Amino acid and carbohydrate composition were similar to those reported for the bovine material. The porcine platelet aggregating factor was found to have no free sulfhydryl groups or exposed disulfide bonds. Binding of formalin-fixed washed human platelets to the aggregating factor linked to Sepharose was inhibited in 0.5 M NaCl or 2.7 M urea and reversed by the presence of free aggregating factor in a concentration-dependent manner. Ristocetin had little or no discernible effect on binding.

Amino Acids↗
PubMed1978

Comparison of the tine and Mantoux tuberculin tests. Report of the Tuberculin Subcommittee of the Researched Committee of the British Thoracic Association.

Intracutaneous (Mantoux 5 TU) and tine tuberculin tests were performed on the opposite arms of 307 people. The results of each test were read by two independent observers at either 48 or 72 hours. Positive readings were recorded in 59% of the Mantoux tests; induration was 10 mm or more in 34.7% of cases. Positive readings were recorded for 3.9% of the tine tests, and a further 15.5% were recorded in the doubtful category. The tine test is unsuitable for epidemiological use because of the high proportion of negative and doubtful results in people positive on the Mantoux test. For the same reasons its usefulness in clinical practice is very limited.

False Negative Reactions↗
PubMed1978

Intravenous infusion of salbutamol in severe acute asthma.

Out of 62 asthmatic patients admitted to hospital with an acute exacerbation of their disease, those whose symptoms had not sufficiently improved 15 minutes after an initial intensive regimen were randomly allocated to receive an intravenous infusion of either salbutamol 10 microgram/min (20 patients) or aminophylline 1 mg/min (19 patients). During the infusions, which lasted 36 hours, peak expiratory flow rates and spirometric values improved in both groups, but differences between the groups did not achieve statistical significance. Although salbutamol may be infused safely for a prolonged period to patients with acute asthma, it has no particular advantage over aminophylline. Furthermore, in patients who respond poorly to initial intensive treatment the subsequent infusion of a bronchodilator may not increase the rate of recovery from the rate that would occur naturally.

Acute Disease↗
PubMed1978

The metabolic effects of inhaled salbutamol.

1 The metabolic effects of salbutamol (5 mg) given by intermittent positive pressure breathing have been studied in eight patients with airflow obstruction. 2 No changes in plasma nonesterified fatty acids, triglyceride, glucose, insulin or cortisol were seen 1 and 4 h after administration. 3 It is concluded that inhaled salbutamol does not cause the unwanted metabolic effects reported with oral or parenteral administration, and that this is a further indication for this route of administration.

Adult↗