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Biomedical subjects

C M Cameron

Publications and source records attributed to C M Cameron.

At least 37 records · Page 2Linked to original sources
PubMed1987

Metabolic basis for the diabetogenic action of growth hormone in the obese (ob/ob) mouse.

The ob/ob mouse responds predictably to chronic treatment with large doses of pituitary GH with marked hyperglycemia and decreased glucose tolerance. The purpose of the present study was to characterize the metabolic alterations produced by GH that lead to this diabetogenic response in the ob/ob mouse in order to determine whether this animal might serve as a useful model for the study of the cellular mechanisms involved in the diabetogenic action of GH. Female ob/ob mice were treated sc for 3 days with either saline or 200 micrograms/day S-carboxymethylated human GH (RCM-hGH), a diabetogenic GH derivative lacking significant growth-promoting or insulin-like activities. Six hours before the start of the experiment, the animals were given a sc injection of 2 micrograms dexamethasone and deprived of food. RCM-hGH treatment produced marked increases in fasting blood glucose and plasma insulin concentrations, but had no effect on plasma glucagon or serum insulin-like growth factor I levels. It had no effect on liver glycogen level or in vitro hepatic glucose production in the absence or presence of pyruvate and lactate added to the incubation medium. By contrast, the in vitro stimulatory effects of insulin on [14C] glucose oxidation by isolated soleus muscle or segments of parametrial fat were greatly attenuated by RCM-hGH treatment, without changes in rates of basal glucose oxidation. This change in peripheral tissue responsiveness to insulin does not appear to involve glucose transport, since the in vitro stimulation by insulin of 3-O-[14C]methylglucose transport into isolated diaphragm muscle was not altered by RCM-hGH treatment. Moreover, the RCM-hGH-induced reduction in adipose tissue responsiveness to insulin does not appear to be mediated by a reduction in insulin binding, since [125I]iodoinsulin binding to adipocytes isolated from RCM-hGH-treated mice was similar to that to cells from saline-treated animals. Interestingly, the reduction in responsiveness to insulin seen with segments of adipose tissue from RCM-hGH-treated animals was not found with isolated adipocytes prepared from such tissue by collagenase digestion. These results suggest that the hyperglycemia and glucose intolerance produced in ob/ob mice by chronic GH treatment result primarily from increased peripheral tissue insulin resistance. Therefore, the ob/ob mouse provides a useful model to elucidate the cellular mechanism(s) of this aspect of the diabetogenic action of GH.

Adipose Tissue↗
PubMed1987

Influence of age on responsiveness to diabetogenic action of growth hormone.

Responsiveness to the growth-promoting action of growth hormone (GH) develops gradually during post-natal life, and as the organism ages, sensitivity to the hormone declines. Our study was undertaken to determine whether there is a similar age-related pattern of sensitivity to the diabetogenic action of purified native human GH (hGH) in the obese (ob/ob) mouse. The ob/ob mouse was used because adults of this strain respond to chronic GH treatment with increases in fasting plasma insulin and blood glucose concentrations and with glucose intolerance. When hGH was given subcutaneously to adult (4-mo-old) female mice at doses of 5, 10, or 25 micrograms/day for 3 days, a significant increase in fasting blood glucose concentration and an impairment in glucose tolerance were produced by the 10-micrograms/day dose. Larger effects were obtained with the 25-micrograms/day dose. A threefold increase in fasting plasma insulin concentration was also produced with this dose of the hormone. By contrast, 25 micrograms/day of hGH had no effect on fasting plasma insulin, blood glucose, or glucose tolerance in 1-mo-old ob/ob mice. When a dose of 100 micrograms/day of hGH was given to 1-mo-old animals, a significant increase in fasting plasma insulin concentration occurred, but again there were no effects on fasting blood glucose or glucose tolerance. Mice 1.5 mo old showed marginal changes in fasting blood glucose and glucose tolerance when given hGH at doses of 25 or 100 micrograms/day. Mice 9 or 12 mo old exhibited responsiveness similar to that of 4-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Antibody response in cattle to oil emulsion rabies and ephemeral fever vaccines.

A stable oil emulsion rabies vaccine with a low viscosity was composed by a formula previously employed for Newcastle disease vaccine. Cattle developed high and sustained antibody levels, and guinea pigs were found to be solidly immune after a single injection of this vaccine. Antibody responses in cattle to 2 oil emulsion ephemeral fever vaccines were not satisfactory after a single injection, and severe local reactions were encountered when booster injections were applied.

Animals↗
PubMed1986

Prolactin actions on casein and lipid biosynthesis in mouse and rabbit mammary gland explants are abolished by p-bromphenacyl bromide and quinacrine, phospholipase A2 inhibitors.

p-Bromphenacyl bromide (BPB) at concentrations of 50 microM and above and quinacrine (50 microM) abolished the actions of prolactin (PRL) on casein and lipid biosynthesis in cultured mouse mammary gland explants. In cultured rabbit mammary gland explants, 100 microM BPB or quinacrine abolished the PRL stimulation of casein synthesis, while 50 microM BPB or 250 microM quinacrine abolished the PRL stimulation of lipid biosynthesis. Since BPB and quinacrine are known to inhibit the enzyme phospholipase A2 (PLA2), it is possible that ongoing PLA2 activity is essential for prolactin to express its actions on at least certain lactogenic processes.

Acetophenones↗
PubMed1986

Comparison of single doses of ketanserin and placebo in chronic stable angina.

Single doses of ketanserin (20 or 40 mg) and placebo were compared in a double-blind cross-over study in 10 patients with chronic stable angina treated with a beta-adrenoceptor antagonist. Ketanserin had no significant effect on the exercise time to angina, the rate of ST segment depression, or the circulatory response to exercise. The 95% confidence limits indicate that ketanserin is unlikely to increase exercise time to angina by more than 20%.

Adrenergic beta-Antagonists↗
PubMed1986

Response of sheep and cattle to combined polyvalent Pasteurella haemolytica vaccines.

The antibody response to various combined polyvalent Pasteurella haemolytica vaccines was studied in sheep and cattle. In sheep, certain oil adjuvant vaccines gave rise to a better antibody response to P. haemolytica than an A1(OH)3-adsorbed vaccine. This finding, however, was not consistent for all serotypes, and with respect to P. multocida, oil adjuvants had no advantage. Furthermore, it was found that the removal of all the culture supernatant fluid during the production process had no deleterious effect on the antigenicity of the product. In cattle, good responses were obtained with both alum-precipitated and A1(OH)3-adsorbed vaccine where all culture supernatant fluid was not removed during the production process. No advantage was gained with oil emulsion vaccines. The degree of immunity afforded to mice and the antibody response to different serotypes of P. haemolytica varied considerably. Further detailed studies with respect to specific serotypes of P. haemolytica are therefore required.

Adjuvants, Immunologic↗
PubMed1986

Immunization of guinea-pigs and cattle with a reduced dose Clostridium chauvoei vaccine produced in a semi-synthetic medium.

A semi-synthetic culture medium and method are described for the production of a reduced dose Clostridium chauvoei vaccine. The vaccine gave excellent results in guinea-pigs, and 2 injections of 2.0 ml protected cattle against challenge with 2 M.L.D. of a virulent culture for at least 12 months. The suitability of C. chauvoei Strain OP64 as a vaccine strain was confirmed.

Animals↗
PubMed1985

Trypsin-resistant forms of human growth hormone have diabetogenic and insulin-like activities.

Although diabetogenic and insulin-like activities are intrinsic properties of the growth hormone (GH) molecule, it has been frequently suggested that the hormone must be proteolytically processed for these activities to be expressed. If this is correct, then derivatives of GH having resistance to appropriate proteolytic attack might not have diabetogenic and/or insulin-like activity. The purpose of the present study was to prepare derivatives of human GH that are resistant to digestion by trypsin and to determine whether they possess diabetogenic or insulin-like activity. Three derivatives were prepared from purified native human GH in which lysine residues were modified with methyl acetimidate, citraconic anhydride or S-ethyl-thioltrifluoroacetate, and one in which arginine residues were modified with camphorquinone-10-sulfonic acid. Comparisons of peptide maps of tryptic digests of these derivatives with that of unmodified human GH indicated that all four were resistant to proteolysis by trypsin. All of these trypsin-resistant forms of human GH were found to possess significant growth-promoting, diabetogenic and insulin-like activities, although all activities were attenuated to some extent in each derivative. The relative potencies of the human GH derivatives in a radioimmunoassay for human GH were somewhat similar to their order of potency in the growth-promoting and diabetogenic assays. These results suggest that if proteolytic processing of the GH molecule is involved in the expression of one or more of its biological activities, such processing probably does not involve a trypsin-like proteinase.

Adipose Tissue↗
PubMed1985

Biosynthetic 20-kilodalton methionyl-human growth hormone has diabetogenic and insulin-like activities.

The anterior pituitary gland produces a 20-kilodalton (kDa) variant of human growth hormone (hGH) that differs from the predominant 22-kDa form of hGH in that amino acid residues 32-46 are deleted. Previous work has suggested that the 20-kDa variant possesses the full growth-promoting and lactogenic activities of 22-kDa hGH but lacks its intrinsic diabetogenic and insulin-like activities. In the present study, recombinant DNA techniques were used to prepare biosynthetic 20-kDa hGH, and some of the biological properties of the purified hGH variant were examined. The biosynthetic 20-kDa hGH variant was found to share the propensity for aggregation exhibited by its native counterpart. Moreover, like the native variant, biosynthetic 20-kDa hGH possessed full growth-promoting activity in the weight gain test in hypophysectomized rats. However, contrary to previous work suggesting that native 20-kDa hGH lacks diabetogenic and insulin-like activities, biosynthetic 20-kDa hGH was found to have substantial diabetogenic activity when administered chronically to ob/ob mice and to possess approximately 20% the in vitro insulin-like activity of biosynthetic 22-kDa hGH on isolated epididymal adipose tissue of hypophysectomized rats. The diabetogenic and insulin-like activities of biosynthetic 20-kDa hGH cannot be ascribed to contamination of the hormone preparation with the 22-kDa form of hGH or with other diabetogenic or insulin-like pituitary peptides. Therefore, the results strongly suggest that diabetogenic and insulin-like activities are also intrinsic properties of the 20-kDa variant of hGH.

Adipose Tissue↗
PubMed1985

Nonmammalian growth hormones have diabetogenic and insulin-like activities.

Purified GHs isolated from ostrich, sea turtle, snapping turtle, bullfrog, Tilapia, and sturgeon were tested for in vivo diabetogenic activity in the hereditarily obese ob/ob mouse and for in vitro insulin-like activity in isolated adipose tissue from hypophysectomized rats. GHs from all species exhibited significant diabetogenic activity, causing fasting hyperglycemia and decreased glucose tolerance when administered at doses of 100 micrograms/day (ostrich, bullfrog, and sturgeon) or 200 micrograms/day (sea turtle, snapping turtle, and Tilapia) for 3 days. Similar responses were obtained when purified human GH was administered at a dose of 10 micrograms/day for 3 days. GHs from most species also exhibited significant insulin-like activity, stimulating increased [14 C]glucose oxidation to 14CO2 by isolated adipose tissue from hypophysectomized rats when employed at concentrations of 50 nM (bullfrog), 250 nM (sturgeon), 500 nM (ostrich), or 2500 nM (sea turtle and Tilapia). Purified human GH gave similar responses at concentrations of 2.5-5 nM in this assay. These results support the hypothesis that diabetogenic and insulin-like activities are intrinsic properties of GH and provide strong evidence that the structural determinants for diabetogenic and insulin-like activities arose early in the evolution of the GH molecule.

Animals↗
PubMed1984

Reduced and S-carboxymethylated human growth hormone: a probe for diabetogenic action.

The biological activity profile of reduced and S-carboxymethylated human growth hormone (RCM-hGH) was determined to establish its suitability for study of the diabetogenic property of hGH. RCM-hGH was found to have greatly attenuated in vivo growth-promoting activity in the 9-day weight-gain test in hypophysectomized rats (approximately 1%) and to have a similar low order of in vitro activity in stimulating amino acid incorporation into the protein of the isolated rat diaphragm. RCM-hGH also only had approximately 1% of the in vitro insulin-like activity of the native hormone on isolated adipose tissue from hypophysectomized rats. In contrast, RCM-hGH retained substantial in vivo diabetogenic activity in the ob/ob mouse, appearing to have approximately 50% of the activity of the native hormone. RCM-hGH was also found to retain significant, although attenuated (25%), in vitro lactogenic activity when tested for the ability to stimulate amino acid incorporation into a casein-rich protein fraction in mouse mammary gland explants. Because RCM-hGH exhibits a high degree of diabetogenic activity, although lacking significant anabolic or insulin-like activities, it will be useful as a "monovalent" probe for the study of the molecular mechanism of the diabetogenic action of GH.

Adipose Tissue↗
PubMed1984

Factors affecting the immunogenicity of Pasteurella haemolytica in mice.

An appreciable level of immunity from intraperitoneal infection with Pasteurella haemolytica was established in mice by using a vaccine prepared in a conventional bacteriological culture medium, with aluminium hydroxide gel as adjuvant. The level of immunity could not be elevated by using bacteria grown in tissue culture media, enriched brain heart infusion broth, the addition of serum to the media or by using bacteria that had been harvested in the logarithmic growth phase. Although various extracts of the bacteria elicited a distinct immunity, the immunogenicity of vaccines containing bacteria could not be enhanced by augmentation with those products. The potential application of the vaccine in cattle and sheep is discussed.

Animals↗
PubMed1984

Formulation of an effective Pasteurella multocida vaccine for sheep.

An effective vaccine for the immunization of sheep against Pasteurella multocida infection was prepared from P. multocida Strain D4 (Type D) and a selected strain of P. multocida Type A. Provided an adequate concentration of bacteria was used, the vaccine thus formulated induced antibodies in sheep that protected mice not only against the vaccine strains but also against infection by a number of heterologous Type A and Type D strains as well as untypable strains. A locally prepared A1(OH)3 gel was found to be an effective adjuvant.

Adjuvants, Immunologic↗
PubMed1984

An improved Corynebacterium pseudotuberculosis vaccine for sheep.

Extensive experiments in mice confirmed that the immunogenicity of a Corynebacterium pseudotuberculosis vaccine could not be significantly improved with the use of various adjuvants. Immunity against C. pseudotuberculosis likewise could not be enhanced by incorporating various immunostimulants into the vaccine or by the use of live vaccines. However, a combination of aluminium hydroxide gel and saponin as adjuvant did have a beneficial effect. This vaccine was tolerated better, and a smaller dose apparently protected sheep more effectively against intralymph node challenge than the currently available alum-precipitated vaccine.

Adjuvants, Immunologic↗
PubMed1983

Effects of prostaglandins on the prolactin stimulation of lipid biosynthesis in mouse mammary gland explants.

The effects of prostaglandins E1 and E2, indomethacin, arachidonic acid, and 8,11,14-eicosatrienoic acid on the rate of (14C)-acetate incorporation into lipids in mouse mammary gland explants were studied. Prostaglandins E1 and E2, as well as their precursors 8,11,14-eicosatrienoic acid and arachidonic acid, inhibited the rate of (14C)-acetate incorporation into lipids, possibly through increased cAMP levels or through end product inhibition of acetyl CoA carboxylase and fatty acid synthetase by long chain fatty acids. Indomethacin at concentrations of 50 micrograms/ml and above significantly reduced the basal rate of 14C-acetate incorporation into lipids, but it did not abolish the prolactin response. Since the prostaglandins, at low concentrations, have prolactin-like actions on RNA synthesis and ornithine decarboxylase activity, and since indomethacin attenuates the actions of prolactin on RNA synthesis, casein synthesis, and ornithine decarboxylase activity, it seems apparent that all of the metabolic actions of prolactin in the mammary gland may not occur via the same primary mechanism.

8,11,14-Eicosatrienoic Acid↗
PubMed1983

Hormonal control of lipid metabolism in mouse mammary gland explants.

Lipid biosynthesis in cultured mammary tissues from mice during midpregnancy was maximally stimulated by the combined actions of PRL, insulin, and a glucocorticoid. The minimal concentration of cortisol that was consistently permissive for the action of PRL on lipid synthesis was 0.1 microgram/ml (2.76 X 10(-7) M). The PRL effect began after 6-8 h of exposure to PRL. The response to PRL was essentially all or none, with 25 ng/ml sufficient for maximal stimulation. Specificity of the PRL effect is suggested by the observation that 1 microgram/ml bovine GH was without effect in cultured mammary tissues. Additionally, PRL had no effect on lipid metabolism in explants of ovarian fat pad, suggesting that the PRL effect in the mammary gland is not a generalized effect on fat cells. The action of PRL in the mammary gland requires both ongoing RNA and protein syntheses, since both actinomycin D and puromycin abolished its effect. The early action of PRL on lipid biosynthesis was specific for the formation of triglycerides, but not other lipid classes studied.

Acetates↗