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Biomedical subjects

J W Craig

Publications and source records attributed to J W Craig.

At least 19 recordsLinked to original sources
PubMed1985

Mechanisms of insulin resistance in cultured fibroblasts from a patient with leprechaunism: resistance to proteolytic activation of glycogen synthase by trypsin.

Post-receptor or post-binding events in the action of insulin have been investigated in cultured skin fibroblasts from an infant with leprechaunism. Both diminished binding of insulin and multiplication-stimulating activity (MSA) to these cells as well as deficits distal to binding were described in a previous publication. Exposure of control fibroblasts to low concentrations (0.001 to 0.01%) of trypsin for one min without glucose in the medium activated the enzyme glycogen synthase; activation was less than that observed with a maximally effective concentration (10(-6) M) of insulin alone. In cells from the patient with leprechaunism, the effect of trypsin was much smaller than in the control fibroblasts. Exposing the control cells to soybean trypsin inhibitor before addition of trypsin prevented activation of glycogen synthase and demonstrated the specificity of the proteolytic action of trypsin. The rates of activation and inactivation of glycogen synthase in vitro were similar in extracts of the control subject's and the patient's fibroblasts and indicated that the enzymes regulating the phosphorylation/dephosphorylation of glycogen synthase were intact in the patient's cells. Total glycogen synthase activity and glycogen content were also indistinguishable in control and leprechaun fibroblasts. These results are compatible with the presence of an abnormality in the structure or availability of the protease substrate from which chemical mediators of insulin action are formed in the patient's cells. Two possible models for a receptor-coupling complex are proposed. Either a mutation in a regulator-substrate unit of the receptor-coupling complexes for insulin and certain insulin-like growth factors or an alteration in the environment of the unit are postulated to explain the findings.

Cells, Cultured↗
PubMed1979

Astrovirus infection in volunteers.

An extract and a filtrate prepared from feces of a child with mild gastroenteritis were shown by electron microscopy to contain numerous astrovirus particles and were given to eight volunteers by mouth. One subject developed diarrheal illness and concurrently shed large amounts of astrovirus in feces, and one other had mild constitutional symptoms with a lower level of virus shedding. Nine other volunteers were given fecal filtrate from the volunteer with diarrhea, and astrovirus shedding subsequently occurred in two of them. The syndrome accompanying virus shedding appeared distinct from that associated with the "W" agent in previous experiments. Thirteen of 16 astrovirus-inoculated subjects subsequently developed a rise in titer of the homologous antibody in serum. It was concluded that astrovirus causes a transmissible infection that is of low pathogenicity for adults. Immunofluorescence of human embryo kidney cells inoculated with astrovirus and shown by electron microscopy to contain 28 nm virus-like particles was used both to detect virus in feces and to assay astrovirus antibody.

Adolescent↗
PubMed1978

Effect of a polynucleotide interferon inducer of fungal origin on experimental rhinovirus infection in humans.

A double-stranded RNA of fungal origin (BRL 5907) was given intranasally to volunteers. Apart from mild local irritancy of the higher dosage, the compound was well tolerated. A double-blind placebo-controlled trial of a three-day course (5 mg per day) of BRL 5907 against challenge with rhinovirus type 4 showed that treatment was associated with a delay in onset of symptoms and a reduction in shedding of virus, but the differences were not statistically significant. Low titers of interferon were found in nasal washings.

Adolescent↗
PubMed1977

Selection of influenza B virus recombinants and their testing in humans for attenuation and immunogenicity.

The selection of influenza B virus recombinants from plaques in bovine kidney cell monolayers is described. Two sets of recombinants were each derived from parents of high and low virulence for humans, respectively. Recombination frequency was apparently high, and reassortment of genes made it possible to obtain attenuated recombinants containing the surface antigens of the virulent parents. Attenuation and immunogenicity were demonstrated in a series of volunteer trials. However, technique proved less satisfactory than for influenza A viruses which periodically undergo antigenic shift and for which there is a wide choice of parent viruses with distinctive surface antigens. In our two influenza B recombinant series there was appreciable antigenic overlap in the neuraminidases of the parents, even though in both cases these were chronologically widely separated. Another marker used was comparative titer at 35 and 38 degrees C. In practice, technical problems might sometimes make it difficult to ensure rapid production of live influenza B vaccines by recombination.

Antibody Formation↗
PubMed1977

A trial of ascorbic acid in the treatment of the common cold.

A randomised controlled trial was carried out to study the effect of 10 g of ascorbic acid taken during the first 2 1/2 days on the symptoms of the common cold. Altogether 1524 volunteers were recruited from a number of working groups in different parts of the country; 482 developed colds. There was no evidence that upper respiratory or general constitutional symptoms were alleviated by ascorbic acid. Among the men who had any colds at all, significantly fewer on active than on placebo treatment had two or more colds; however, this effect was not seen in women. Ascorbic acid is of no value in the treatment of the common cold; its preventive effect, if any, is not such as to justify advising its general use as a prophylactic measure.

Ascorbic Acid↗
PubMed1976

Virulence for man of a human influenza-A virus antigenically similar to "classical" swine viruses.

The newly isolated human influenza-A strain containing swine antigens isolated in New Jersey, U.S.A., was inoculated into six volunteers. Clinical reactions were mild although all volunteers were infected. The longest period for which the virus was excreted was 8 days and the shortest 3 days. In its virulence for man the New Jersey strain was intermediate between a human and animal virus, and was quite clearly more virulent than known swine viruses. It seems possible that the outbreak in the U.S.A. was an isolated event and that the virus will not become established in man.

Antibodies, Viral↗
PubMed1976

Four compounds active against rhinovirus: comparison in vitro and in volunteers.

Four unrelated compounds active against rhinovirus were compared in tissue culture, and three of them were used in volunteers challenged with rhinovirus. The compounds were the triazino-indole SKF 40491, the substituted oxadiazole GLR9-338, the imidazo-thiazole RP L9326, and the guanidine derivative ICI 73,602. The abilities of these compounds to reduce the yield of rhinovirus types 3, 4, 9, and 31 from HeLa cells or fibroblasts were compared, and a sensitive serotype was chosen for each challenge experiment in humans. In doubleblind studies volunteers received intranasal medication before and after the challenge. Daily scoring of symptoms and titration of virus in nasal washings showed that subjects treated with SKF, GL, and RP all shed less virus than their corresponding placebo groups, significantly so in the cases of GL and RP. Clinical reactions were also less severe in volunteers treated with RP.

Adolescent↗
PubMed1975

Trials in man with live recombinants made from A/PR/8/34 (H0 N1) and wild H3 N2 influenza viruses.

A long-term study is described of recombinant influenza viruses produced from the avirulent laboratory strain, A/PR/8/34 (H0 N1), and newly isolated H3 N2 influenza virus variants. A number of H3 H2 recombinants were found to be attenuated for man and capable of inducing antibody formation, and were therefore potentially usable as live vaccines. However, the volunteer trials as a whole suggested that, in this system, there might not be complete segregation of virulence and antigenic characteristics. No H3 N2 recombinants were detected which were non-infective for man, like the A/PR8 (H0 N1) parent, and reciprocal hybrids (H3 N1 and H0 N2) always reflected some of the virulence of the parent from which they had inherited their haemagglutinin. This property is not a feature of mouse influenza.

Animals↗