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Biomedical subjects

L Levine

Publications and source records attributed to L Levine.

At least 109 records · Page 6Linked to original sources

The stimulation of prostaglandin production by transforming growth factor-alpha and 12-O-tetradecanoyl-phorbol-13-acetate or 1-oleoyl-2-acetyl-glycerol is synergistic.

Stimulation of prostaglandin production in C-9 rat liver cells by transforming growth factor (TGF)-alpha was synergistic with that of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). TGF-alpha and TPA synergized the release of radiolabelled compounds from [3H]arachidonic acid prelabelled C-9 cells. 1-Oleoyl-2-acetyl-glycerol (OAG) and TGF-alpha also synergized prostaglandin production in the C-9 cells suggesting that the tumor promoter was mimicking the physiological activator of protein kinase C, 1,2-diacylglycerol. TGF-alpha and TPA also synergistically stimulated arachidonic acid metabolism by NRK-49F rat kidney cells. In A-549 human lung carcinoma cells, TGF-beta, but not TGF-alpha, stimulated arachidonic acid metabolism synergistically with TPA.

Animals↗

Stimulation of prostaglandin E2 production by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters in macrophages and its inhibition by cycloheximide.

The effects of TPA (12-O-tetradecanoylphorbol 13-acetate)-type and non-TPA-type tumor promoters on prostaglandin E2 production by peritoneal macrophages of rats were examined. Among the TPA-type tumor promoters, aplysiatoxin was most potent in stimulating prostaglandin E2 production followed by dihydroteleocidin B, teleocidin, TPA and debromoaplysiatoxin. Prostaglandin E2 production by aplysiatoxin treatment was stimulated at doses up to 0.1 ng/ml. Palytoxin, a non-TPA-type tumor promoter, also stimulated both prostaglandin E2 production and the release of radioactivity from [3H]arachidonic acid-labeled macrophages. However, the dose required for the expression of these effects by palytoxin was up to 3 pg/ml. It was suggested that the tumor promoters are associated with the activity to stimulate arachidonic acid metabolism, irrespective of their type. Cycloheximide, a protein synthesis inhibitor, inhibited both prostaglandin E2 production and the release of radioactivity from prelabeled macrophages stimulated either by the TPA-type tumor promoters or by the non-TPA-type tumor promoter. It is possible that the tumor promoters may induce the synthesis of some proteins responsible for the stimulation of arachidonate metabolism.

Acrylamides↗

Influence of heat stress and acclimation on maximal aerobic power.

Thirteen male volunteers performed cycle ergometer maximal oxygen uptake (VO2max tests) in moderate (21 degrees C, 30% rh) and hot (49 degrees C, 20% rh) environments, before and after a 9-day heat acclimation program. This program resulted in significantly decreased (P less than 0.01) final heart rate (24 bt X min-1) and rectal temperature (0.4 degrees C) from the first to last day of acclimation. The VO2max was lower (P less than 0.01) in the hot environment relative to the moderate environment both before (8%) and after (7%) acclimation with no significant difference (P greater than 0.05) shown for maximal power output (PO max, watts) between environments either before or after acclimation. The VO2max was higher (P less than 0.01) by 4% after acclimation in both environments. Also, PO max was higher (P less than 0.05) after acclimation in both the moderate (4%) and hot (2%) environments. The reduction in VO2max in the hot compared to moderate environment was not related to the difference in core temperature at VO2max between moderate and hot trials, nor was it strongly related with aerobic fitness level. These findings indicate that heat stress, per se, reduced the VO2max. Further, the reduction in VO2max due to heat was not affect be state of heat acclimation, the degree of elevation in core temperature, or level of aerobic fitness.

Acclimatization↗

The protective effect of dietary fish oil on murine lupus.

Dietary marine lipids markedly reduce the severity of glomerulonephritis and its associated mortality in inbred strains of mice developing autoimmune disease, a model for human systemic lupus erythematosus. We report here the influence of varying the dose of menhaden oil and the timing of its administration on the mortality of female (NZB x NZW) F1 mice. After ingesting 25 wt% menhaden oil (MO) for periods of 1.5 weeks to 12 months, there was a stable content of tissue n-3 fatty acids, with total n-3 fatty acids of 28% and 35% in spleen and liver, respectively. The extent of protection from mortality was dependent on the dose of MO with marked protection at doses of 11 to 25%, marginal protection at 5.5% and no protection at 2.5% MO. Delay in the institution of MO until ages 5 or 7 months still resulted in large reductions of mortality. Conversely, institution of a MO diet from 6 weeks until ages 5 to 7 months followed by a change to beef tallow resulted in little protection. Serum levels of 4 cyclooxygenase products were reduced ranging from 26 to 76% in mice fed MO diets, compared to mice fed beef tallow, based on radioimmunoassay. The degree of reduction of mortality on different doses of MO was correlated best with tissue levels of C22:5, and levels of C20:5 and C22:6 were similar at high and low doses of MO, suggesting that levels of 22:5 may be related to the protective effects of marine lipids on autoimmune disease.

Animals↗

Alpha and beta human transforming growth factors stimulate prostaglandin production and bone resorption in cultured mouse calvaria.

Human alpha and beta transforming growth factors (TGF-alpha and TGF-beta) stimulated the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvaria in organ culture. Significant stimulation of bone resorption by TGF-alpha was observed with a concentration of 0.2 ng/ml (35 pM) and by TGF-beta with 0.2 ng/ml (8.0 pM). Enhanced production of PGE2 and bone resorption stimulated by either TGF-alpha or TGF-beta were both inhibited by indomethacin. We conclude that TGF-alpha and TGF-beta are potent and powerful stimulators of the resorption of mouse bone by a mechanism that involves the enhanced local production of PGE2.

6-Ketoprostaglandin F1 alpha↗

Stimulation of arachidonic acid metabolism by different types of tumor promoters.

Skin tumor-promoting agents, including the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, such as diterpine phorbol esters, teleocidin and aplysiatoxin, and a non-TPA-type tumor promoter (the newly described palytoxin, present in the coelenterate of the genus Palythoa), stimulated arachidonic acid metabolism by rat liver cells in culture. Palytoxin was 1000-3000 times more effective than TPA-type tumor promoters. The stimulations of arachidonic acid metabolism by palytoxin and the TPA-type tumor promoters were synergistic, whereas the stimulations among the TPA-type tumor promoters were not. The stimulation of arachidonic acid metabolism by palytoxin was synergistic with that of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta (TGF-beta). An antiserum to the EGF-receptor that blocks EGF binding partially inhibited the synergistic responses to palytoxin and EGF and palytoxin and TGF-alpha, whereas an antiserum to the EGF-receptor that does not block EGF binding or a non-immune rabbit serum did not.

Acrylamides↗

Skeletal muscle metabolism during exercise is influenced by heat acclimation.

The influence of heat acclimation on skeletal muscle metabolism during submaximal exercise was studied in 13 healthy men. The subjects performed 30 min of cycle exercise (70% of individual maximal O2 uptake) in a cool [21 degrees C, 30% relative humidity (rh)] and a hot (49 degrees C, 20% rh) environment before and again after they were heat acclimated. Aerobic metabolic rate was lower (0.1 l X min-1; P less than 0.01) during exercise in the heat compared with the cool both before and after heat acclimation. Muscle and plasma lactate accumulation with exercise was greater (P less than 0.01) in the hot relative to the cool environment both before and after acclimation. Acclimation lowered (P less than 0.01) aerobic metabolic rate as well as muscle and plasma lactate accumulation in both environments. The amount of muscle glycogen utilized during exercise in the hot environment did not differ from that in the cool either before or after acclimation. These findings indicate that accumulation of muscle lactate is increased and aerobic metabolic rate is decreased during exercise in the heat before and after heat acclimation; increased muscle glycogen utilization does not account for the increased muscle lactate accumulation during exercise under extreme heat stress; and heat acclimation lowers the aerobic metabolic rate and muscle and blood lactate accumulation during exercise in a cool as well as a hot environment.

Adaptation, Biological↗

Leukotriene production in gerbil brain after ischemic insult, subarachnoid hemorrhage, and concussive injury.

A leukotriene-like immunoreactivity was measured by radioimmunoassay in the gerbil forebrain following ischemia and reperfusion, subarachnoid hemorrhage (SAH), or nonlethal concussive brain injury. In each paradigm an increase in immunoreactivity levels was found. Peak levels were reached 15 to 30 minutes after each insult, and slowly returned to baseline over the next 24 hours. The study supports the suggestion that cerebral vessels and circulating blood are capable of producing leukotrienes, and that a major source of production is a nonvascular component within gray matter, possibly the cortical neuron. Leukotrienes may play a role in the pathophysiology of cerebral edema formation, cerebral vasospasm, seizure activity, and other central nervous system abnormalities. These studies are the first to demonstrate leukotriene production in gerbil brain following SAH or concussive brain injury.

Animals↗

The stimulations of arachidonic acid metabolism by recombinant murine interleukin 1 and tumor promoters or 1-oleoyl-2-acetyl-glycerol are synergistic.

Recombinant murine IL 1 stimulated arachidonic acid metabolism by rat liver cells (the C-9 cell line) and squirrel monkey smooth muscle cells, and in the presence of tumor promoters this stimulation was synergistic. In the rat liver cells that had been prelabeled with [3H]arachidonic acid, the release of 6-keto-PGF1 alpha and arachidonic acid also was stimulated by the IL 1, and this release was synergistic in the presence of TPA. 1-Oleoyl-2-acetyl-glycerol (OAG) stimulated prostaglandin production, and IL 1 synergized the prostaglandin production in the presence of OAG. OAG and TPA mimic the endogenous activator of protein kinase C, 1,2-diacylglycerol, and therefore IL 1 may amplify arachidonic acid metabolism during signal transmission processes.

Animals↗

Determinants of mother-infant interaction in adolescent mothers.

Mother-infant interactions of adolescent and nonadolescent mothers are compared, and the impact of maternal age, ego development, education, and child care support on these interactions is examined. Thirty primiparous, white, lower- to middle-class mothers (half less than or equal to 17 years) and their healthy full-term infants (8 months) were studied. Interactions were videotaped during face-to-face interactions and teaching sessions. Child care support and ego development were assessed. During face-to-face interactions, only one difference was found between adolescent and nonadolescent mothers: nonadolescent mothers showed more positive affect toward infants. During teaching, nonadolescent mothers talked more, showed more positive affect toward infants, and demonstrated tasks more often. Individual differences during face-to-face interactions were more related to mothers' ego development and support whereas teaching interactions were mostly associated with maternal age. Thus, maternal age was a stronger predictor of interactive style during teaching. This may partially explain noted cognitive deficits in infants of teenage mothers. However, individual differences among all mothers in ego development, education, and support were significantly related to interactions. Thus, teenage mothers with less education and support and lower ego development may represent a higher risk subgroup of adolescent mothers providing less optimal care-giving environments for their infants.

Adolescent↗

Minimizing risk of adverse reactions to mydriatic agents in binocular indirect ophthalmoscopy.

To minimize the risk of adverse side effects from mydriatics during binocular indirect ophthalmoscopy, a procedure was developed which intentionally starts with a dose significantly less than an ED99. Using a clinically effective diameter of greater than 7 mm as a criterion, I found that 1 drop of 0.5% tropicamide (T) constituted an ED74 (N = 46). When 1 drop of 2.5% phenylephrine (P) was added, this increased to an ED93 (N = 27). If present results can be generalized, then 1 drop of T, supplemented at 30 minutes with 1 drop of P, if necessary, should produce satisfactory dilatation in approximately 90% of the subjects.

Adult↗

Melittin-stimulated arachidonic acid metabolism by cultured malignant human epidermal keratinocytes.

Upon melittin stimulation, cultured SCC-13 keratinocytes release prostaglandins E2, F2 alpha, 6-keto-F1 alpha, thromboxane B2, leukotriene B4, and 6-sulfido-peptide-containing leukotrienes (SRS) into serum free medium. Release of prostaglandins E2, F2 alpha, and SRS, normalized to cell protein, is 3- to 10-fold higher from rapidly growing than confluent cultures. Cells growing with hydrocortisone in the medium produce approximately twice the level of the cyclooxygenase-mediated metabolites PGE2 and PGF2 alpha as those without hydrocortisone, but similar levels of the lipoxygenase-mediated metabolite SRS. The results demonstrate the potential utility of squamous carcinoma lines for investigating biochemical pathways of arachidonic acid metabolism in keratinocytes.

Arachidonic Acid↗

Synthesis of compounds with properties of leukotrienes C4 and D4 in gerbil brains after ischemia and reperfusion.

6-Sulfidopeptide-containing leukotriene-like immunoreactivity was synthesized in gerbil forebrains after bilateral common carotid occlusion and reperfusion. At 5, 10, or 15 minutes of ischemia, concentrations increased significantly and became more marked on reperfusion. Immunoreactivity was highest in forebrain gray matter and was below the detection limit of the assay in brain regions remote from the zone of ischemia. In vitro experiments with vascular cells and organ cultures of cerebral arteries indicate that the cerebral blood vessel wall is not a major source of biosynthetic activity in the brain. These experiments demonstrate leukotriene biosynthesis by the brain. Because synthesis occurs during ischemia and reperfusion and because leukotrienes are potent vasoconstrictors and promoters of tissue edema, they may play a role in the pathophysiology of cerebral ischemia.

Animals↗

Serologic and immunochromatographic detection of oxygenated polyenoic acids in Euglena gracilis var. bacillaris.

Acetone extracts of Euglena gracilis Klebs var. bacillaris Cori contain several lipoxygenase and cyclooxygenase products as measured by radioimmuno-assay. Three times more of the serologically active products are found in cells grown in the dark than in cells grown in the light. Lack of coincidence of their retention times on high performance liquid chromatography with authentic oxygenation products of arachidonic acid suggest that most of the serologically active compounds are derivatives of polyenoic fatty acids other than arachidonic acid. Several fractions react with anti-12-hydroxyarachidonic acid (an antiserum that recognizes mono- and di-hydroxyarachidonic acids). Three of these fractions have UV absorption spectra characteristic of conjugated trienes.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗