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Biomedical subjects

C C Smith

Publications and source records attributed to C C Smith.

At least 217 records · Page 12Linked to original sources
PubMed1978

Properties of beta-adrenergic receptors in untreated and butyrate-treated Hela cells.

HeLa cells contain receptors on their surface which are beta-adrenergic in nature. The binding of (-)-[3H]dihydroalprenolol is rapid, reversible, stereospecific and of relatively high affinity. The HeLa cells also contain an adenylate cyclase which is activated by (-)-isoproterenol greater than (-)-epinephrine greater than (-)-norepinephrine. The adenylate cyclase of HeLa is also activated by guanyl-5'-ylimidodophosphate (Gpp(NH)p), a nonhydrolyzable analogue of GTP. Inclusion of both (-)-isoproterenol and Gpp(NH)p leads to approximately additive rather than synergistic activation of adenylate cyclase. After treatment of HeLa cells with 5mM sodium butyrate there is an increase in the number of beta-adrenergic receptors, but not in their affinity, which is reflected in an increased ability of (-)-isoproterenol to activate adenylate cyclase. Other properties of the beta-adrenergic receptor including association and dissociation rates, temperature optimum of adenylate cyclase and response to Gpp(NH)p are relatively unaffected by butyrate pretreatment of the cells.

Adenylyl Cyclases↗
PubMed1978

Growth of Mycobacterium lepraemurium in nonstimulated and stimulated mouse peritoneal-derived and bone marrrow-derived macrophages in vitro.

Mycobacterium lepraemurium cells were found to multiply in normal mouse peritoneal-derived and bone marrow-derived macrophages in vitro. Whereas activated peritoneal-derived macrophages demonstrated marked bacteriostasis for M. lepraemurium, significant bactericidal activity was exhibited by activated bone marrow-derived macrophages. However, only a small proportion of the bacterial were killed by activated bone marrow-derived macrophages with subsequent and enhanced bacteria growth. It is suggested that a rapid turnover of monocytes in active lesions is required to control mycobacterial infections in vivo. These results would suggest that careful consideration be given to the choice of the host cell in studies involving obligate intracellular parasites.

Antigens, Bacterial↗
PubMed1977

Influence of cyclophosphamide and 4-ketocyclophosphamide on mouse limb development.

Many studies have been performed on the in vivo teratogenicity of cyclophosphamide, and there is uncertainty whether the parent compound or P-450 generated alkylating metabolite(s) is the proximal teratogen(s). We have examined the influence of cyclophosphamide and a metabolite, 4-ketocyclophosphamide, on mouse limb development. Pregnant mice were injected with 10, 15 or 20 mg/kg of cyclophosphamide on days 9 to 11 of gestation. Hindlimb buds were maximally sensitive to 20 mg/kg of cyclophosphamide at 9 A.M. on day 11, and the predominant malformations formed were preaxial ectrodactyly and hemimelia. Hindlimb buds of the same gestational age exposed to cyclophosphamide in vitro responded identically to controls in morphology and uptake of 3H-thymidine and 35SO4. Exposure to 4-ketocyclophosphamide in culture, however, resulted in the formation of limbs with a "hemimelic" appearance and distal limb reduction, and with reduced uptake of 3H-thymidine and 35SO4. These findings support the position that the P-450 generated metabolite(s), and not the parent compound, is the proximal teratogen(s).

Animals↗
PubMed1977

Effects of cytosine arabinoside on in vivo and in vitro mouse limb development.

When pregnant mice were exposed to 40 mg per kg of cytosine arabinoside (ara-C) on days 10 to 12 of gestation, adactylous limbs with large, distally located blisters were found when the fetuses were examined on day 18. Embryonic limbs exposed transplacentally under identical conditions and explanted to culture exhibited the same morphological abnormality as did limbs exposed directly in culture to 0.1 to 1 microgram per ml of ara-C. Two noncytotoxic analogues of ara-C, uridine arabinoside (ara-U) and hypoxanthine arabinose (ara-HX), had no influence on morphological differentiation of limbs in vitro. Ara-C alone caused a dose-related decrease in uptake of 3H-thymidine and 35SO4 in cultured limb buds. Production of this morphologically distinct malformation in vitro will allow detailed biochemical investigations on the effect of ara-C limb ectodermal-mesenchymal interactions.

Abnormalities, Drug-Induced↗
PubMed1977

Induction of functional beta-adrenergic receptors in HeLa cells.

HeLa cells contain beta-adrenergic receptors that are characterized by specific binding of I[3H]dihydroalprenolol, increased 3':5'-cyclic AMP production in intact cells after incubation with l-isoproterenol, and increased adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in the presence of l-isoproterenol. After cells were cultured with butyrate, the number of beta-adrenergic receptors, cyclic AMP production in intact cells, and adenylate cyclase activation by l-isoproterenol were increased severalfold over those of untreated cells. The increase involved the induction of synthesis of new receptor molecules with identical affinities for l-[3H]-dihydroalprenolol; all three processes were blocked by cycloheximide and actinomycin D. This induction was relatively specific for butyric acid and only the closely related short-chain fatty acids, propionic and valeric acids, were capable of partially inducing the same effect. In contrast to induction of beta-adrenergic binding sites, there was no increase in basal or fluoride-activated adenylate cyclase activity, indicating that the beta-adrenergic receptor and adenylate cyclase and different molecules that may be controlled separately.

Adenylyl Cyclases↗
PubMed1977

Mutagenic studies of folic acid antagonists.

Compounds that compete with folic acid (folic acid antagonists [FAAs]) become limited in their usefulness in the treatment of leukemia, malaria, and bacterial infections by the rapid development of resistance. Assays of the plasma levels of certain of these FAAs led to the observation, in about 25% of the determinations, that a higher density of growth of Streptococcus faecium var. durans (ATCC 8043) was obtained at an FAA concentration just below the completely inhibitory level than at one-half this concentration. This and other considerations suggested that FAAs may act not only as selective agents for resistant organisms but also as mutagens. Seven FAAs including amethopterin, pyrimethamine, trimethoprim, chlorguanide triazine, an experimental quinazoline, WR-158,122, and two experimental triazines, WR-99,210 and WR-38,839, were tested for mutagenicity in the Salmonella reversion assay developed by Ames et al. (1975). All were found to be negative for strains TA1535, TA1537, TA1538, TA98, and TA100, both with and without microsomal activation. These compounds were then tested as mutagens for three traits in the folic acid-requiring S. faecium. FAAs were shown to cause mutations to folic acid independence, rifampin resistance, and FAA resistance. It is postulated that the FAAs induce mutations by causing thymine deprivation in the folic acid-requiring host.

Culture Media↗
PubMed1977

An analysis of three mixed dentition analyses.

The accuracy of prediction of three mixed dentition analyses was compared. Hixon and Oldfather's method was found to be the most accurate. A simplified version of the analysis obviates referral to a table, allowing assessment of the size of the unerupted teeth prior to eruption of the lateral incisor.

Bicuspid↗
PubMed1976

Phylogenetic variability of serum lipids and lipoproteins in non-human primates fed diets with different contents of dietary cholesterol.

The response of serum lipids and lipoproteins to different levels of dietary cholesterol (0.05% to 1.5% w/w) was measured in six nonhuman primate species. Relative response of serum cholesterol in different species, measured in terms of response, index, varied with dietary cholesterol concentration. The overall response for the different diets allowed ranking of the species as follows: Squirrel is greater than green is greater then spider is approximately thesus is approximately patas is greater than chimpanzee The serum cholesterol response was reflected not only in an increase in beta + pre-beta-lipoprotein cholesterol but also in alpha-lipoprotein cholesterol, with significant differences among species in the amount of cholesterol transported in the lipoprotein classes.

Animals↗
PubMed1976

Serum lipid and lipoprotein responses of six nonhuman primate species to dietary changes in cholesterol levels.

The response of serum lipids and lipoproteins to different levels of cholesterol in the diet was studied in chimpanzee (Pan troglodytes), rhesus (Macaca mulatta), green (Cercopithecus aethiops), patas (Erythrocebus patas), squirrel (Saimiri sciurea) and spider (Ateles sp.) monkeys. Five animals of each species were fed increasing amounts of dietary cholesterol (0.05% to 1.5% W/W) for 3-week periods; between each experimental diet, the animals were fed a basal diet without cholesterol for a similar period. Serum cholesterol response of different species measured in terms of response index (area under the time-concentration curve above basal value) varied with the dietary cholesterol content and showed a significant interspecies difference at 0.5% dietary cholesterol (1.8 mg/kcal) level. The overall response for the different diets allowed ranking of the species as follows: squirrel greater than green greater than spider approximately equal to rhesus approximately equal to patas greater than chimpanzee. The serum lipoprotein response was reflected not only in an increase in beta-lipoprotein but also in alpha-liprotein with significant differences among species in the amount of cholesterol transported in the lipoprotein classes. Challenging the animals with dietary cholesterol seems to be an essential step for determining inter- and intraspecies differences.

Animals↗