Biomedical subjects

L A Scheving

Publications and source records attributed to L A Scheving.

At least 37 records · Page 2Linked to original sources

PubMed1990

A preliminary report of circadian effects of interleukin-2 (IL-2) on the activity of enzymes of intermediary metabolism of mice.

Since it previously has been reported that IL-2 has profound circadian dependent effects upon DNA synthesis in the liver of mice (Scheving et al., 1988; Tsai et al., 1988) the effects of IL-2 on enzyme activities were studied. The objective was to determine the effect of IL-2 when administered at different times to mice who were fed ad libitum, and standardized to 12 h of light alternating with 12 h of dark. Three groups were injected intraperitoneally with either 1 or 4 mg/kg of IL-2, one group was given the vehicle only. The treatment time for each dose and the vehicle was a 2 h into the light for one group and the other was at 2 h into the dark span. Subgroups of 5 mice were killed 4, 8, 12, 16, 20, 24, and 30 h after each treatment, livers were taken and frozen to await preparation and analysis of enzyme activities by our standard procedures. When treatment was in the light span IL-2 had no statistically significant effect on enzymes of lipid, carbohydrate or amino acid metabolism. On the contrary when treatment was given in the dark span IL-2 produced statistically significant increases in enzymes of glycolysis, and lipid synthesis beginning 8 h after treatment (changes ranged from 20 to 43%) with both the higher and lower doses (higher doses always yielded higher activities), and these activities continued to increase through the 24 h post-treatment span (changes ranged from 42 to 64%). At 30 h, activities were returning to normal levels. Amino acid metabolism, on the other hand, was decreased during these post-treatment times (the range of decrease was from 18 to 44%). Thus, we report for the first time that the duration of time, pathway affected, as well as the magnitude of the effect seen and the dosage of IL-2 were all circadian-stage dependent even with two time point samplings. We believe, however, that these two time points represent different critical extremes in liver metabolism, but studies with denser sampling are planned. Interleukin-2 was generously supplied by Cetus Corp. of Emeryville, CA.

Alanine Transaminase↗

PubMed1989

Epidermal growth factor receptor of the intestinal enterocyte. Localization to laterobasal but not brush border membrane.

Interaction of epidermal growth factor (EGF) with its specific receptor (EGFR) was explored in the intact rat small intestine and in highly purified isolated enterocyte membrane preparations. Despite the fact that the EGF ligand is known to be present at physiological concentrations within the intestinal cavity, no significant binding of the ligand to the brush border surface was observed. Instead, binding of EGF to the EGFR was confined to other membrane populations, and correlation of ligand interaction with the laterobasal membranes (LBM) was nearly perfect (p less than 0.001) across a special equilibrium gradient enriched in brush border and LBM but devoid of intracellular membranes. Specific binding to another minor population of intracellular membranes that migrated to a position less dense than typical endoplasmic reticulum-Golgi vesicles on equilibrium gradients was also observed. Immunocytochemical exposure of intestine to EGFR antibody confirmed the localization of the EGFR to LBM and intracellular membranes. As estimated from the intensity of the staining, there may be immunologically active but nonbinding receptor species in the intracellular membrane compartment. Thus, despite the secretion of EGF into the intestinal lumen, the growth and maturational effects of EGF probably result from a specific interaction between EGF and EGFR solely at the laterobasal surface of the enterocyte. The functional role of the intracellular membrane species of EGFR, which remains to be established, may involve a source of inactive receptor that can be rapidly recruited and transferred to the LBM surface under changing environmental conditions.

Animals↗

PubMed1989

Circadian variation of epidermal growth factor receptor in mouse liver.

The liver undergoes a biochemical and morphological circadian transformation. In this paper, we document circadian variation in the binding parameters of the hepatic epidermal growth factor receptor (EGFR). Liver membranes were prepared from ad libitum fed or fasted male CD2F1 mice killed at different circadian phases at 4 h intervals. Bmax (maximum binding) and Kd (dissociation constant) varied in a rhythmic fashion. The range of change for Bmax along the 24 h time scale was 423%. For Kd, it was 162%. Both peaked late in the dark span, and decreased late in the light span. Fasting and EGF treatment reduced Bmax and the amplitude of circadian variation.

Animal Nutritional Physiological Phenomena↗

PubMed1987

Thymosin alpha 1: amino acid homology with peptide T from the human immunodeficiency virus envelope.

Thymosin alpha 1 has many effects on immune function and its absence in primary immunodeficiency states produce a clinical presentation similar to the one encountered in acquired immune deficiency syndrome (AIDS). Human immunodeficiency virus (HIV), the etiologic agent of AIDS, binds to T4 helper/inducer lymphocytes through specific surface receptors which include the CD4 glycoprotein. Octapeptide T, a component of the HIV envelope, mediates the binding of HIV to its receptor. In this report, we draw attention to the similarity between the amino acid sequence of thymosin alpha 1 and peptide T and its analogues. This similarity can produce a cross-reactivity between thymosin alpha 1 and HIV and may be a factor in the pathophysiology of the acquired immuno-deficiency syndrome.

Amino Acid Sequence↗

PubMed1987

Circadian-dependent response in DNA synthesis to epidermal growth factor in spleen, bone marrow, and lung and in mitotic index of corneal epithelium in ad libitum-fed and fasted CD2F1 mice.

The effect of epidermal growth factor (EGF) on DNA synthesis in the spleen, bone marrow, and lung and on the mitotic index in the corneal epithelium was investigated in CD2F1 mice that were standardized on an LD 12:12 cycle and either fed ad libitum or fasted for 24-34 hr. EGF brought about decreases in DNA synthesis in both the bone marrow and spleen in ad libitum-fed male mice. Moreover, the degree of response and the duration of time it took for the decreases to become statistically significant were circadian-stage dependent. The response brought about by EGF on DNA synthesis in the lung also was circadian-stage dependent, but it was an increase and occurred much later than in the spleen or bone marrow. The maximum decreases brought about by EGF in spleen and bone marrow occurred at 13 hr after EGF treatment, being 37% and 28%, respectively. The maximum increase in DNA synthesis in the lung was 116% and was recorded 33 hr after treatment, but the first statistically significant increase (35%) was recorded 28 hr after treatment. Under the conditions of this study, fasting diminished the overall level of DNA synthesis in the bone marrow, spleen, and lung. We conclude, however, that sampling was too limited to draw definitive conclusions regarding the persistence of a DNA synthesis rhythm in fasting and the effect that EGF has on the fasting rhythm. There was no apparent effect on fasting on the mitotic index of the corneal epithelium.

Animals↗

PubMed1986

Effect of thioacetamide on the incorporation of [3H]-thymidine into DNA of 13 tissues and on the mitotic index of the corneal epithelium of BD2F1 in male mice while taking into consideration circadian variation.

An investigation was done to assess the effect of a single intraperitoneal (ip) injection of thioacetamide on the incorporation of [3H]TdR into DNA of 13 different tissues and on the mitotic index of the corneal epithelium of mice. Seven-week-old CD2F1 mice, who had been standardized to 12 hours (hr) of light alternating with 12 hr of darkness, and fed ad libitum were used. The experimental design took into consideration the circadian variation that characterizes cell proliferation in all of the tissues studied. This was done by killing subgroups of seven animals every 6 hr for 96 hr. Thirty minutes prior to killing all mice were injected ip with 25 mu Ci of [3H]-thymidine and its incorporation into DNA was determined. The tissues of all thioacetamide and saline treated mice showed marked circadian variation in DNA synthesis. Thioacetamide treatment brought about significant (P less than 0.05) stimulation of DNA synthesis in the liver and kidney thus confirming, but extending an earlier finding. Moreover, the data showed for the first time that DNA synthesis in the bone marrow and spleen and colon were markedly statistically significantly stimulated at specific times after treatment. Synthesis of DNA in the thymus, lung, testes, tongue, esophagus, duodenum, rectum and the mitotic index in the corneal epithelium were not statistically significantly altered by thioacetamide treatment. A preliminary study also was carried out to explore what effect multiple treatment with epidermal growth factor (EGF) had on DNA synthesis in thioacetamide treated mice. Mice were killed 36 hr after thioacetamide treatment, but were treated with EGF which began 15 hr after the thioacetamide was administered and this was repeated at 18, 21 and 24 hr (50 micrograms/mouse/treatment). Under the conditions of this study EGF significantly (P less than 0.05) depressed DNA synthesis 76% in the liver, 64% in the thymus, 22% in the spleen, 30% in the duodenum and 24% in the esophagus. A histological analysis of the livers of four EGF treated and four non-EGF treated mice was done, but no consistent differences in terms of necrosis, inflammation or regeneration were observed between the two groups.

Acetamides↗

PubMed1985

Sex differences in circadian rhythms of several variables in lymphoreticular organs, liver, kidney, and corneal epithelium in adult CD2F1 mice.

In this paper data resulting from an investigation into the influence of sex on selected circadian rhythms in lymphoreticular organs, liver, kidney, and corneal epithelium of adult CD2F1 mice are reported. Increased organ weight, total DNA and RNA in the spleen, total DNA and [3H thymidine [( 3H]TdR) incorporation into DNA in the thymus, and [3H]TdR incorporation into DNA in the liver and bone marrow in female mice compared to male littermates is demonstrated. In contrast, kidney weight and [3H]TdR incorporation into DNA as well as the corneal epithelium mitotic index are greater in male mice. Except for the corneal epithelium mitotic index and total splenic RNA and DNA, circadian rhythmicity in the variables studied is validated using the cosinor method of rhythmometric analysis in male but not in female mice. The lack of sinusoidal rhythmicity in female mice is presumed to be due to asynchrony of estrous cycling between mice within this group. Moreover, a differential organ response to exogenous testosterone enthanate is reported. The administration of this hormone suppresses [3H]TdR incorporation into DNA in the thymus and liver but not in the spleen or bone marrow at 18, 42, or 72 hr after injection.

Androgens↗

PubMed1985

Epidermal growth factor enhances guanylate cyclase activity in vivo and in vitro.

Epidermal growth factor (EGF) increases DNA synthesis and cell division both in vivo and in vitro. The mechanism by which EGF increases growth and DNA synthesis is unknown. Since the intracellular messenger cGMP stimulates DNA synthesis, the present investigation was designed to determine if EGF might have part of its mechanism of action through activating guanylate cyclase [EC 4.6.1.2], the enzyme that catalyzes the formation of cGMP. EGF enhanced soluble and particulate guanylate cyclase activities as well as cGMP levels 2- to 3-fold in hypophysectomized and nonhypophysectomized tissues both in vivo and in vitro. EGF increased guanylate cyclase activity 0.5 h after ip injection in mice, and this increased activity was still present 12 h later. Guanylate cyclase activity was increased to a greater extent secondary to EGF in hypophysectomized cecum compared to nonhypophysectomized cecum. Dose-response curves revealed that maximal stimulation of guanylate cyclase by EGF occurred at 1 nM. There was no augmented guanylate cyclase activity when the concentration of EGF was decreased to 0.01 nM. The data in this investigation suggest that guanylate cyclase may play a role in the mechanism of action of EGF.

Animals↗

PubMed1984

Effect of fasting on circadian rhythmicity in deoxyribonucleic acid synthesis of several murine tissues.

These studies were done with CD2F1 adult mice that had been standardized to 12 hours of light alternating with 12 hours of darkness to determine what effect a 24-hour fast had on circadian rhythms in DNA synthesis of 10 different regions of the gut, as well as in the pancreas, liver, thymus, spleen, bone marrow, lung and testis. The mitotic index of the corneal epithelium also was studied. The overall responses varied rather dramatically. For example, in the different regions of the gut the response ranged from no statistically significant change in the colon to a strong statistically significant decrease in DNA synthesis in the cecum. In short, one cannot generalize about the effect of short-term fasting on the entire gut, but when there was any statistically significant effect, it always was a decrease. The spleen was the only tissue that showed no statistically significant response in DNA synthesis. In the bone marrow, however, a statistically significant increase in DNA synthesis was recorded at 8 and 24 hours after fasting began. In the lung there was a rather dramatic increase in DNA synthesis at 8 hours, but this was followed by decreases of 37 and 55% at 16 and 24 hours, respectively. There was a statistically significant increase of 83% in the mitotic index 24 hours after the fasting began. The data clearly demonstrate the necessity of considering circadian variation when evaluating the effects of fasting on cell proliferation.

Animals↗

PubMed1984

Circadian dependent effect of epidermal growth factor, insulin and glucagon on hepatic pyruvate kinase and malic enzyme of mice.

The influence of epidermal growth factor (EGF), 0.75 micrograms g1; insulin, 1.5 micrograms g-1; glucagon, 1.25 micrograms g-1 and their combinations on the activities of hepatic pyruvate kinase (PK) and malic enzymes (ME) was monitored. Male CD2F1 mice were treated toward the end of the light or dark periods, 9 or 23 hours after lights on (9 or 23 HALO), and subgroups of six mice were killed at 4, 8 or 12 hr post-treatment. PK and ME activities from control mice were well characterized by cosine curves. The PK activity was maximal when ME activity was minimal at the transition from light to dark (9 HALO plus 4 hr) and PK was at a minimum when ME was highest (23 HALO plus 4 hr). Both enzymes were influenced by at least one peptide hormone, and the effects were strongly circadian-stage dependent. The only effect attributed to EGF was an increase of PK activity (23%) 12 hr after injection at 23 HALO. PK activity was increased by insulin (23%) at 23 HALO (4 hr after injection), but not at 9 HALO, and decreased (17%) by glucagon 12 hr after injection at 9 HALO. Several reductions in PK activity in response to various combinations of peptides were observed, and appeared to be caused by glucagon but influenced by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Primary amino acid sequence similarity between human epidermal growth factor-urogastrone, human pancreatic secretory trypsin inhibitor, and members of porcine secretin family.

Sequence similarities are detected between human epidermal growth factor-urogastrone, human pancreatic secretory trypsin inhibitor, and members of the secretin family of gastrointestinal hormones, particularly gastric inhibitory peptide. These similarities suggest a common evolutionary origin for these proteins and a possible functional relationship, as evidenced by the ability of human epidermal growth factor-urogastrone and human pancreatic secretory trypsin inhibitor to form a complex with protease and the ability of human epidermal growth factor-urogastrone and secretin family members to inhibit gastric acid secretion.

Amino Acid Sequence↗

PubMed1983

Chronobiology of the intestinal tract of the mouse.

This paper summarizes recent and continuing work on circadian rhythms in the alimentary tract of rodents; these include: (1) cell proliferation, (2) activities of intestinal enzymes, and (3) behavioral aspects of spontaneous feeding and drinking. All regions of the intestinal tract show marked circadian behavior in cell proliferation. The roles of the light-dark cycle and meal timing in synchronizing such rhythms are discussed as well as the influence of epidermal growth factor, insulin, glucagon, and ACTH 1-17. Attention is called to the potential importance of these rhythms to basic research and medicine. Other circadian rhythms in the alimentary tract are reviewed briefly, such as those characterizing a host of intestinal enzymes, monosaccharide transport, and the height and width of the villi. Many of these have been shown to be cued to a feeding schedule; however, a number of the enzyme rhythms persist for one or two cycles in fasting animals, and this also is the case for the cell-proliferation rhythms. After having been acclimated to a circadian feeding schedule (within a range of 23-30 hr), rodents can on subsequent days anticipate the food an hour or more prior to its arrival. Some enzymes behave in a similar manner in that their activities increase prior to the expected intake of the daily food. These anticipatory response rhythms are under endogenous control, since both will persist in the fasted animal and both will free run when a mouse is placed under constant conditions. Somehow these animals are able to measure circadian intervals of time. This challenges the concept that the oscillations seen in enzyme activities are simply a passive consequence of feeding and fasting, respectively.

Adrenocorticotropic Hormone↗

PubMed1982

Circadian stage-dependent effects of insulin and glucagon on incorporation of [3H]thymidine into deoxyribonucleic acid in the esophagus, stomach, duodenum, jejunum, ileum, caecum, colon, rectum, and spleen of the adult female mouse.

Insulin and glucagon were injected ip at four different circadian states into separate subgroups of female adult BALB/Cann mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control subgroups were injected with saline. Four, 8, 12, and 18 h after each of the four injections, subgroups of seven mice that had been injected 30 min earlier with tritiated thymidine ([4H]TdR) were killed; a total of 336 mice were used. The incorporation of [3H]TdR into DNA of the esophagus, stomach, duodenum, jejunum, caecum, colon, rectum, and spleen was subsequently determined. The results demonstrate for the first time that both hormones affect the incorporation of [3H]TdR into DNA in all of the examined organs but in different ways and at different circadian stages. The effects of these hormones were complex, but several generalizations emerged. 1) Insulin tended to increase the incorporation of [3H]TdR into DNA in the examined organs, whereas glucagon tended to decrease it. 2) Insulin was more effective in stimulating the incorporation of [3H]TdR into DNA when injected either at the end of the dark span or the beginning of the light span, as opposed to the end of the light span or the beginning of the dark span. 3) Insulin had its greatest effect on [3H]TdR incorporation into DNA in the glandular stomach and rectum, whereas glucagon had its greatest effect on the colon and spleen. 4) The effects of both insulin and glucagon were different from those of epidermal growth factor, as revealed in a similar study done by us. Our results suggest that insulin, glucagon, and epidermal growth factor play important roles in the control of growth of various endodermally derived organs.

Animals↗

PubMed1981

Circadian stage-dependent effects of epidermal growth factor on deoxyribonucleic acid synthesis in ten different organs of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian stages into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness: light, 0600-1800 h; dark, 1800-0600 h), five animals were killed at 4, 8, and 12 h after the EGF injection; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 muCi [3H]thymidine. Incorporation of [3H]thymidine into the DNA of the aorta, lung, liver, cornea, testes, kidney, parotid, thymus, spleen, and bone marrow as well as the mitotic index of the corneal epithelium was determined. The results indicate that EGF may play a role in the positive control of growth of many of these tissues, especially the aorta, lung, liver, and cornea. EGF may also play a role in inhibiting growth of the thymus, spleen, and bone marrow. Moreover, the stimulatory effect of EGF on the growth of the various tissues appears to be especially enhanced in mice injected at 1500 h and killed 4 h later at 1900 h.

Animals↗

PubMed1980

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular salivary glands of mice was injected ip at five different circadian phases into separate sub-groups of adult male CD2F1 mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control groups were injected only with the carrier substance. Four, 8, and 12 h after each of the five injection times, subgroups of five mice were killed. Thirty minutes before sacrifice, each mouse was injected ip with 24 mu Ci tritiated thymidine ([3H]-TdR). Incorporation of [3H]TdR into the DNA of the duodenum, jejunum, ileum, cecum, colon, and rectum was determined. The results demonstrate for the first time that EGF has a stimulatory effect on DNA synthesis in these tissues, particularly in the colon and rectum. Under the conditions of this study, the stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were more dramatic than those in the three regions of the small intestine; in fact, DNA synthesis in the latter was occasionally statistically significantly decreased, particularly for mice killed during the dark phase. Stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were noticed as early as 4 h after injection; however, maximal stimulation occurred 8 and 12 h post injection.

Animals↗

PubMed1979

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the tongue, esophagus, and stomach of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian phases into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness), five animals were killed, 4, 8, and 12 h after the injection of EGF; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 muCi [3H]thymidine. Incorporation of [3H]-thymidine into the DNA of the tongue, esophagus, and stomach was determined. The results demonstrate for the first time that EGF has a strong in vivo stimulatory effect on DNA synthesis in the tongue, esophagus, and stomach (studies on other areas of the gut have not yet been completed). Under the conditions of the study, stimulatory effects occurred as soon as 4 h subsequent to injection; however, maximal stimulation occurred for all three tissues 8 h after injection. Twelve hours after injection, the levels of DNA synthesis in all tissues were generally returning to normal levels found in the control animals. The results suggest circadian variation in susceptibility to EGF in the different tissues.

Animals↗

PubMedDate not supplied

Effects of epidermal growth factor on deoxyribonucleic acid synthesis and stomach weight in hypophysectomized adult mice.

Epidermal growth factor (EGF) or saline was administered intraperitoneally to hypophysectomized adult male CD2F1 mice or intact controls at 0700 hr. Subgroups of mice were killed at 4, 8, or 12 hr after injection. EGF was shown to stimulate [3H]TdR incorporation into DNA into several organs as previously reported. The response to EGF was found to be enhanced in both hypophysectomized and fasted mice. Differences in [3H]TdR incorporation into DNA, corneal epithelium mitotic index, RNA in pancreas and kidney of hypophysectomized and intact mice are reported. EGF was shown to result in stomach enlargement due to increased luminal contents in both hypophysectomized and intact mice.

Animals↗

PubMedDate not supplied

Effect of epidermal growth factor (EGF) on [3H]TdR incorporation into DNA in ad lib fed and fasted CD2F1 mice.

The effect of EGF on the incorporation of [3H]TdR into DNA (DNA synthesis) was determined in the esophagus, liver, pancreas, and kidney in mice standardized to 12 hours (hr) of light alternating with 12 hr of darkness. A question asked was whether intraperitoneally administered EGF could alter the circadian patterns of DNA synthesis in these organs. The most marked effects of EGF were: an increase in DNA synthesis but only after a specific duration of time after treatment, ranging from 8 to 23 hr, which differed for each tissue, a similarity in the response of the esophagus in both ad lib fed and fasted mice, but not in the response of the liver, where the stimulatory effect of EGF observed in fed mice was dramatically reduced in fasted ones, and an advance in the phasing of the circadian rhythm in DNA synthesis of the esophagus by about 12 hr. In addition, no sex differences in fasted animals were found under the conditions of this study.

Animals↗