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Biomedical subjects

G E Quinby

Publications and source records attributed to G E Quinby.

At least 19 recordsLinked to original sources
PubMed2000

Intradermal granulocyte-macrophage colony-stimulating factor alters cutaneous antigen-presenting cells and differentially affects local versus distant immunization in humans.

We hypothesized that intradermal delivery of granulocyte-macrophage colony-stimulating factor (GM-CSF) would alter the number and differentiation state of local antigen-presenting cells and thereby alter immunization strength at that site in humans. GM-CSF or placebo was administered intradermally on consecutive days prior to contact sensitization at that site. In GM-CSF-treated skin, epidermal CD1a(+)S100(+) Langerhans cells were reduced in number and had altered morphology, while the number of dermal CD1a(+), HLA-DR(+), and S100(+) cells was increased. In the deep dermis CD68(+) macrophages were increased. Expression of the APC activation markers CD40 and ICAM-1 was also increased in the dermis. Subjects were sensitized to DNCB through GM-CSF- or placebo-pretreated skin and to DPCP through untreated skin. Subjects immunized through GM-CSF-treated sites exhibited 64% greater elicitation responses to DNCB than placebo-treated subjects. GM-CSF-treated subjects also showed 43% lower responses to DPCP than placebo-treated subjects. The difference between DNCB (local) and DPCP (distant) responses was significantly greater for GM-CSF-treated subjects than for placebo responses (n = 8, P < 0.05). Therefore, local immunization site pretreatment with intradermal GM-CSF enhances immunization efficiency at that site.

Adult↗
PubMed1999

Expression of MFA1 and STE6 is sufficient for mating type-independent secretion of yeast a-factor, but not mating competence.

The yeast a-factor mating peptide and its transporter Ste6 are normally expressed only in MATa haploid cells. The a-factor is initially produced as a 36- or 38-residue peptide precursor and must undergo extensive post-translational processing to produce an active 12 amino-acid lipopeptide. To better understand the steps required for Ste6-dependent a-factor transport, we have reconstituted a-factor synthesis and transport in MATalpha haploids and MATa/alpha diploids. Ste6 and a-factor were stably expressed in MATalpha and MATa/alpha cells and the ectopically expressed a-factor was correctly processed. In addition, Ste6 was able to transport a-factor from all cell types, indicating that once expressed no other MATa-specific functions are required. However, despite significant levels of a-factor secretion, MATalpha cells are unable to support efficient mating.

ATP-Binding Cassette Transporters↗
PubMed1997

An amino terminal prosequence is required for efficient synthesis of S. cerevisiae a-factor.

The Saccharomyces cerevisiae a-mating pheromones are 12 amino acid lipopeptides whose secretion is dependent on the ABC transporter, Ste6p. The pheromones are synthesized as 36 and 38 amino acid precursors that terminate in a CaaX box (C is Cys, a is an aliphatic residue, and X is the C-terminal amino acid). Posttranslational processing of the a-factor precursors includes at least 5 events. C-terminal processing of the CaaX box includes farnesylation of Cys, removal of the -aaX residues, and methylation of the cysteine alpha-carboxyl group. The N-terminal steps involve proteolytic cleavages that remove the prosequences. In this report, we have investigated the role of posttranslational modification in the generation of functional a-factor. Wild type, mutant and chimeric forms of a-factor have been expressed in yeast and assessed for their abilities to serve as sources of functional a-factor. We have found that although modification of the CaaX box is necessary, it is not sufficient to generate bioactive a-factor. The amino terminal prosequences are also required. Deletion of these sequences reduces intracellular levels of a-factor resulting in sterility. Glutathione-S-transferase (GST)-a-factor fusions undergo CaaX box processing and membrane localization, but are not substrates for the N-terminal proteases and fail to interact with Ste6p. These results suggest that the amino terminal precursor sequences play a direct role in the generation of functional a-factor.

ATP-Binding Cassette Transporters↗
PubMed1989

5-HETE: uptake, distribution, and metabolism in MDCK cells.

The interaction of (S)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE) with Madin-Darby canine kidney (MDCK) cells was investigated to determine whether this lipoxygenase product might influence tubular epithelial function. When incubated with arachidonic acid, MDCK cells failed to synthesize any 5-HETE. However, MDCK cells can take up 5-HETE to a much greater extent than either 12- or 15-HETE. 5-HETE uptake occurred from both the apical and basolateral surfaces and was not saturated at concentrations up to 10 microM. Much of the 5-HETE was incorporated into phospholipids, primarily phosphatidylcholine and phosphatidylethanolamine. After a 1-h incubation 5-HETE was found to be localized in either the microsomal and/or plasma membrane of MDCK cells. After pulse labeling for 1 h, MDCK cells released 35% of 5-HETE compared with 10% of the incorporated arachidonate during the next 24 h, indicating a much more rapid turnover of newly incorporated 5-HETE. When MDCK cells were incubated with 5.0 microM 5-HETE, their capacity to produce prostaglandin E2 was reduced greater than 50% in as little as 5.0 min. Since 5-HETE enters epithelial phospholipids and reduces prostaglandin production, it apparently has the capacity to modulate renal function if it is released in the proximity of the tubular epithelium during inflammatory reactions.

Animals↗
PubMed1987

Effects of maternal dietary protein on the mandibular growth of fetuses from diabetic dams.

The effects of maternal diabetes on the mandibles in the fetuses of dams given a normal (20% protein) diet vs those given a high protein (40% protein) diet were studied. On day 9, the controls, groups 1 and 3, were injected with citrate buffer and fed a 20% and 40% protein diet, respectively. Groups 2 and 4 were injected with 40 mg/kg B.W. of streptozotocin and pair-fed with groups 1 and 3 with a 20% and 40% protein diet, respectively. On day 22, fetuses were removed. Dissected mandibles were weighed and analyzed for DNA, protein, Ca and hydroxyproline contents. Some dams in each group were injected with either 45Ca or 14C proline to study 45Ca uptake and collagen synthesis. The body and mandibular weights of the fetuses from diabetic (D) dams were smaller than those of the non-diabetic (ND) group in both diets. The protein and hydroxyproline contents of the mandible in the D 20% group was less than the ND. Hydroxyproline content from the D 40% group was less than the ND. The Ca content in the D 40% group was less than the ND. The present study indicates that metabolism in the bone of fetuses whose D dams were fed a high protein diet is affected beneficially in some parameters but not in others.

Animals↗
PubMed1986

Chronic caffeine intake by rat dams during gestation and lactation affects various parts of the neonatal brain.

Timed-pregnant rats were randomly divided into 2 groups on day 13 of gestation. Group 1 received a 20% protein diet. Group 2 was pair-fed to group 1 with a 20% protein diet containing caffeine (1 mg/100 g body weight). At parturition, the dams of each group were continued on their respective diets until day 22 postpartum. At the time of weaning (day 22), only male rats were continued in the study. At this time, rats from both groups were fed the control diet containing 20% protein. On day 57 and 58, rats were killed, the brains divided into six areas, and DNA, RNA and protein contents were measured. In certain areas of the brain, weight, cholesterol, DNA, RNA and protein contents were different even long after returning to the caffeine-free control diet. The present study demonstrates that even if a relatively small amount of caffeine is taken during gestation and lactation, a time during which the growth rate is greater than in any other period of life, certain areas of the brain may be affected. These findings suggest that future central nervous system impairment may be expressed later in life in these offspring.

Animals↗
PubMed1985

Effects of orally-administered caffeine on the growth of tooth germs in protein-energy malnourished newborn rats.

Lactating dams with 8 suckling pups were fed either a 6 or 20 per cent protein diet from the birth of the pups to day 15. Pups were divided into caffeine and non-caffeine groups and, every other day between days 3 and 13, were either intubated with caffeine (1 mg/100 g body wt) dissolved in 0.1 ml physiological saline solution, or 0.1 ml saline solution as a control. At day 15, the weight of incisors and molar germs, hydroxyproline content, collagen synthesis and calcium contents were determined. Nutritional factors exercised consistent effects on all the parameters, but effects attributable to caffeine intubation were minor. There was lower molar weight in the 20 per cent protein group with caffeine, and collagen synthesis of incisor and molar germs in the caffeine and non-caffeine animals in the 6 and 20 per cent group were different. These parameters showed a significant interaction between nutrition and caffeine. Thus the direct administration of a small amount of caffeine to newborns causes only slight effects on tooth-germ development under some nutritional conditions.

Administration, Oral↗
PubMed1985

Effects of oral caffeine intubation on bones in protein-energy malnourished newborn rats.

Lactating dams with 8 suckling pups were fed either a 6% or a 20% protein diet from the birth of the pups to day 15. The pups were divided into caffeine and noncaffeine groups. Every other day between days 3 and 13, pups were either intubated with caffeine (1 mg/100 mg) dissolved in 0.1 ml physiological saline solution, or 0.1 ml saline solution as a control. On day 15, mandible and long bone weights, DNA, protein and calcium contents, collagen synthesis and 45Ca uptake in these bones of the pups were studied. Nutritional factors exercised consistent effects on all the studied parameters, but there was no difference in effects attributable to caffeine intubation, except the increased collagen synthesis in the long bones of the group with 6% protein diet with caffeine as compared to noncaffeine members of the same dietary group. We concluded that the direct administration of a relatively small amount of caffeine to newborns causes minor effects on bone development under certain nutritional conditions.

Animals↗
PubMed1985

Effects of orally administered caffeine on cellular response in protein energy-malnourished neonatal rat brain.

The purpose of this study was to determine the effects of caffeine on growing rats and how protein energy malnutrition can modify these potential effects. Caffeine (1,3,7-trimethylxanthine) is not only the most commonly consumed, neurally active stimulant in our daily lives, but it is widely used in the management of apnea in the premature neonate. One group of dams (20%) (n = 6) was begun on a 20% protein diet ad libitum. The second group (6%) (n = 4) was begun on a 6% protein diet. A third group (20% + C) (n = 4) was pair-fed to group 1 (20%) with the 20% protein diet, but beginning on day 3 the pups received 10 mg/kg body weight of caffeine via intragastric feeding needle every other day. The fourth group (6% + C) (n = 5) was pair-fed with group 2 (6%) with the 6% protein diet and the pups received 10 mg/kg of caffeine in the same manner as the 20% + C group from day 3. Although the 6% protein diet was associated with the expected reduced body and brain growth, there were no additional growth alterations associated with caffeine administration in either the 20% or 6% diet groups. This growth failure was accompanied by the expected reductions in total whole brain DNA, RNA, protein, and cholesterol content regardless of whether caffeine was received or not. Effects of caffeine which were similar in both diet groups included an increase in brain RNA content and concentration and an increase in the RNA/DNA ratio. However, there were differential effects of caffeine seen depending on diet group assignment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Theophylline effects on cellular response in protein-energy malnourished neonatal rat brain.

The present study employed an animal model in an attempt to document effects on brain growth of long-term exposure to theophylline in the presence or absence of malnutrition. One group of dams was randomly divided into half. One-half was fed a 20% protein diet and the other half a 6% protein diet. Similarly, a second group of dams was also randomly divided into two groups. These were pair-fed with rats of the first group, receiving diets comparable to those in group one but to which theophylline was added in amounts calculated to provide daily doses of 2 mg/100 g of body weight. Theophylline supplementation in the dams' 6% protein diet decreased the body weight of the pups consistently from d 3 to the end of the study at d 15 in comparison to the non-theophylline group. In contrast, the presence of theophylline in the control diet increased the body weight of the pups at d 15 compared with that of the non-theophylline group. Brain weight was essentially identical in the normal controls and the normally nourished group given theophylline. No difference in brain weight was noted between the malnourished group and the malnourished group given theophylline. We found a significant reduction in DNA content per brain or per mg of brain weight in the normally nourished group given theophylline compared with non-theophylline group. DNA values per mg of brain weight from the controls that received theophylline were not different from either malnourished group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗