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Biomedical subjects

J Koppel

Publications and source records attributed to J Koppel.

At least 37 records · Page 2Linked to original sources

Subdiabetogenic streptozocin treatment impairs preimplantation development of mouse embryos.

To estimate the significance of insulin in the regulation of preimplantation embryo growth, female mice received a single subdiabetogenic dose of streptozocin (65 mg/kg intraperitoneally) 8-11 days or 14-17 days before fertilization. Mean glycaemia levels and the number of embryos per mouse did not differ significantly between the streptozocin-treated and control groups. Morphological analysis of preimplantation embryos collected on day 3 of pregnancy revealed significant changes in the distribution pattern of preimplantation embryo stages recovered from streptozocin-treated females. Continuous insulin treatment of streptozocin-treated mice improved the impaired development of preimplantation embryos only in short-lasting experiments. After a long subdiabetic period (14-17 days) the incidence of degenerated embryos was increased in both streptozocin-treated groups. It can be concluded that the subdiabetic state in female mice impairs preimplantation embryo development which could partly be prevented by insulin treatment.

Animals↗

Immunocytochemical localization of cyclin/proliferating cell nuclear antigen (PCNA) in fertilized eggs of mice.

Immunolocalization of cyclin/PCNA (proliferating cell nuclear antigen) was performed with monoclonal antibody using immunogold methods on ultrathin cryosections of fertilized mouse eggs. Immunolabeling in pronuclei was checked 20, 22, 24 and 26 h after HCG injection. A relation between onset of pronuclei migration (early S-phase) and appearance of colloidal particle clusters was found. Afterwards, (mid S-phase) the increase of labelling and the localization of cyclin/PCNA were found throughout the pronuclei, except in the nucleolar bodies. Lower labelling appeared at the time of close reciprocal pronuclei contact (late S-phase). It is concluded that bulk and distribution of cyclin/PCNA in pronuclei is closely related to the progression of first interphase after fertilization.

Animals↗

The effect of administration of estradiol and testosterone on body growth of young male rats.

The influence of estradiol and testosterone on body growth of young male Wistar rats was investigated. In the first experiment, estradiol was given to intact ad libitum fed male rats at 32, 37 and 42 days of age. Moreover, two untreated groups of animals were used: one was fed restrictedly according to the food intake of animals receiving estradiol and another was fed ad libitum. The animals were sacrificed at 47 days of age. Both untreated groups of animals achieved significantly higher body weight and length of tibia than estradiol treated animals. Also the growth of the tail of untreated animals was more intensive than that of estradiol treated animals. In the second experiment, estradiol was given to intact ad libitum fed male rats at 30, 35 and 45 days of age. Moreover, testosterone was given to a half of these animals at 45, 50 and 55 days of age. The animals were sacrificed at 60 days of age. Administration of testosterone significantly increased the growth of the tail and tibia in comparison to the animals which did not receive testosterone after estradiol administration. The results of the present study show that the inhibitory effect of estradiol on body growth of young male rats is not only the result of decreased food intake and that testosterone can improve the skeletal growth of male rats altered by previously given estradiol.

Age Factors↗

[Glutamate dehydrogenase and glutamine synthetase activity in the digestive tract in lambs in relation to age].

Developmental dynamics was investigated in the activity of glutamate dehydrogenase (GDH, E.C. 1.4.1.2.-4) and glutamine synthetase (GS, E.C. 6.3.1.2) in different parts of the digestive tract of lambs, in dependence on the age from 10 to 90 days; the goal of these investigations was to elucidate in greater detail the role of the above enzymes in nitrogen metabolism. The activity of GDH, and of the coenzymes NADH and NADPH, was followed in the digesta because simple organisms (bacteria, fungi, plants) have two glutamate dehydrogenases: they differ from each other by coenzyme specificity, unlike GDH from animal sources which can utilize both NADH coenzyme and NADPH coenzyme (Fahien et al., 1965; Frieden, 1964). The following activities of GDH and GS were found out in trials with lambs at the age of 10, 20, 30, 40 and 90 days, as to the different parts of digestive tract: in the tissues of rumen, omasum, reticulum, spleen, duodenum, jejunum, ileum, int. caecum and colon the activity of GDH (NADH) varied from 0.031 to 0.305 nkat/mg dry matter, in the digesta from 0 to 2.92 nkat/mg dry matter. An investigation of GDH (NADH, NADPH) dynamics in the digesta of lambs showed the relatively high activity of GDH (NADH) in the digesta of colon at the age of 10 days and that of GDH (NADPH) in the digesta of int. caecum. The activity of GDH (NADH) was also found to be high in the digesta of int. caecum at the age of 20 days. In that period the activity of GDH (NADH, NADPH) in the digesta of rumen, omasum and reticulum was zero.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Developmental tissue expression and phylogenetic conservation of stathmin, a phosphoprotein associated with cell regulations.

Stathmin is a 19-kDa phosphoprotein presumably involved in regulations of cell proliferation, differentiation, and functions as an intracellular relay for extracellular signals activating diverse second messenger pathways. Antisera prepared against the whole protein or against two peptides (residues 15-27 and 134-149) recognized the two isoforms (alpha and beta) of stathmin in their different phosphorylated states on immunoblots. Also, the possible existence of a family of stathmin-related proteins is suggested by the detection with some sera of proteins of 17, 21, and 60 kDa in brain. Stathmin and its diverse molecular forms were detected in all mouse tissues tested, in varying concentrations. Depending on the tissue, it is 2-100 times more abundant in the neonate than in the adult. It is most abundant in brain at both developmental stages, the protein levels being paralleled by the expression of the corresponding mRNA as detected with a specific cDNA probe. Antibodies directed against the rat protein also reacted with stathmin-like proteins in the brain of other mammals, birds, reptiles, amphibians, and some fish species, and the various isoforms could be recognized on immunoblots. In conclusion, our results suggest that stathmin is most likely involved in two distinct types of regulations: 1) "developmental" regulations, related to cell proliferation, differentiation, and maturation, and 2) "functional" regulations mostly at the adult stage, and typically in the nervous system. In addition, stathmin is also phylogenetically well conserved at least in vertebrates. Together, these observations support the proposed ubiquitous nature and general importance of stathmin in biological regulations.

Aging↗

A single cDNA encodes two isoforms of stathmin, a developmentally regulated neuron-enriched phosphoprotein.

Stathmin, a 19-kDa neuron-enriched soluble phosphoprotein, has been recently proposed as an ubiquitous intracellular relay for the diverse extracellular signals regulating cell proliferation, differentiation, and functions through various second messenger pathways (Sobel, A., Boutterin, M.C., Beretta, L., Chneiweiss, H., Doye, V., and peyro-Saint-Paul, H. (1989) J. Biol. Chem. 264, 3765-3772). Internal sequences of the protein from rat brain were determined after purification by two-dimensional polyacrylamide gel electrophoresis, electrotransfer onto Immobilon, and in situ proteolysis. Oligonucleotide mixtures based on these sequences were used to clone a cDNA for stathmin from a rat PC12 cell lambda gt 10 library. The deduced amino acid sequence reveals partial homologies with the coiled coil structural regions of several intracellular matrix phosphoproteins. Using this cDNA as a probe, we show that the expression of stathmin mRNA parallels that of the protein during brain ontogenesis, reaching a maximum at the neonatal stage. In vitro translation of the derived cRNA yielded all the known molecular forms of stathmin, namely its alpha and beta isoforms in their unphosphorylated and phosphorylated states. Thus, a single cDNA codes for both biologically relevant isoforms of the protein, indicating that they differ by co- or post-translational modifications.

Adrenal Gland Neoplasms↗

Circadian changes in the RNA content of rat hypothalamic nuclei in relation to food intake.

The ribonucleic acid (RNA) and protein content of the ventromedial hypothalamic nuclei (VMH), the lateral hypothalamic areas (LHA) and the cortex (C) of adult male Wistar rats followed free access to food and water were determined at 6-hour intervals (at 6.00, 12.00, 18.00 and 24.00 h); the RNA and protein content of the suprachiasmatic nuclei (SCN) were determined at 12.00 and 24.00 h. The RNA content of the VMH, LHA and SCN differed at various intervals; in the cortex it did not alter significantly. The highest RNA concentration in the VMH was recorded at 18.00 h and in the LHA at 24.00 h, after which, in both areas, it fell. The lowest RNA content in the LHA and the VMH was found at 12.00 h. In the SCN, the RNA concentration at 24.00 h was significantly higher than at 12.00 h. The protein content did not alter significantly during the circadian cycle in any of the structures examined.

Animals↗

RNA content of neurons in the ventromedial nuclei and lateral hypothalamic area relative to feeding status.

The total RNA content of hypothalamic and cortex neurons in relation to the feeding status of adult male Wistar rats was studied. Experimental conditions including food deprivation (12 and 24 hours) and relative satiation (short-term refeeding, glucose or glycerol administration) changed in different ways the total RNA content of the neurons in the ventromedial hypothalamic nuclei (VMH) and in the lateral hypothalamic area (LHA) with respect to fasting or satiety. Only the long-term absence of food (24 hours) significantly increased the total RNA content of the VMH cells, while the RNA content of the LHA neurons significantly decreased in both the 12 and 24 hr fasted rats compared with those fed ad lib. The sixty minute free access to food after 12 or 24 hours of fasting fully reversed these changes. The short-term food intake significantly increased the RNA content of the LHA cells of the 12 and 24 hr fasted animals while the total RNA content of the VMH neurons significantly decreased only in the 24 hr fasted rats. The effect of glucose and glycerol administration on the RNA content of the LHA neurons (in 12 hr fasted rats) was similar to the effect of refeeding. One hour after giving glucose (1 g/kg b.wt.) or glycerol (300 mg/kg b.wt.) the total RNA content in the LHA neurons significantly increased. No changes in RNA content were observed in the neurons of the cortex when comparing the experimental and control rats. The results demonstrated the close relationship between the RNA content of the hypothalamic neurons and the feeding status.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of bovine growth hormone in infant rats from reduced litters.

The objective of this study was to determine the effects of growth hormone on body growth and the content of RNA, DNA and protein in liver, brain and heart muscle in rat pups from reduced nests. Suckling rats raised in litters of 4 youngs were daily injected from 3rd to 28th day of life with 1 microgram of bGH/g body weight. Our results show that GH administration evoked higher body weight gain and increase of tail length after 23rd day of life. There was significant increase of liver content of nucleic acids and protein. This GH-responsivity of pups from reduced nests might be related to differences in their metabolic profile and accelerated somatic and psychosocial development in comparison to normal youngs.

Animals↗

Effects of bovine growth hormone in suckling lambs.

The objective of this study was to determine the effects of bovine growth hormone (bGH) on body growth of suckling lambs. Suckling Merino lambs (fed on milk replacer from 4th day of life) were daily injected from 10th to 38th day of life with 80 micrograms bGH/kg b.w. Only insignificant increase of body weight was observed after 4 weeks of GH treatment. After 31st day of life body weight gain in the experimental lambs was significantly higher. It can be concluded that bGH increases body weight gain of lambs in 2nd month of life. It is probable that growth rate of sucklings is limited only by biological and biochemical capabilities of the organism and it can be hardly influenced by exogenous hormonal manipulation.

Animals↗

Plasma insulin and glucose in suckling and ruminating lambs after peroral administration of glucose and propionate.

An identical volume of water solutions: 1) glucose 5.56 mmol/kg b.w., or 2) sodium propionate 5.56 mmol/kg b.w., was given perorally to sucklings (6 weeks) and weaned lambs (10 weeks). The maximum increase of glycemia and the highest insulin concentrations were observed 60-90 min after glucose administration in both groups of lambs. Plasma insulin of suckling and weaned lambs was increased within 60 min after propionate infusion. It can be concluded that propionate is a potent insulin secretagogue in sucklings as well as in ruminating ones. However, glucose is probably the most effective stimulus for insulin release in both groups of lambs.

Administration, Oral↗

Effects of ovine prolactin in infant rats.

The objective of this study was to determine the effects of ovine prolactin (oPRL) on body growth and the content of RNA, DNA and protein in liver, brain and heart muscle in rat pups. Suckling rats were daily injected from 3rd to 28th day of life with 1 microgram of oPRL/g body weight. Our results show that oPRL administration evoked higher body weight gain up to 8th day of life (p less than 0.05). There was significant (p less than 0.05) increase of DNA liver content and significant decrease (p less than 0.001) of RNA/DNA ratio in the hepatocytes. The findings suggest that prolactin influences growth rate of rats in the early postnatal period of life.

Animals↗

Food intake of infant rats after intraperitoneal administration of insulin.

The effects of intraperitoneal insulin on the food intake have been determined in infant rats up to weaning. It was found that intraperitoneal (IP) insulin reduced the milk intake of 13 and 17 day-old pups for three hours after treatment. In 5, 9 and 24 day-old pups the food intake was not significantly changed after IP insulin administration. Only in 28 day-old rat pups IP insulin induced an increase of food intake. Since subcutaneously (SC) administered insulin gave rise to short-term hyperphagia in 24 day-old rat pups we assessed the effects of SC versus IP insulin on the blood glucose level. Blood glucose was lower 3 hours after SC administration compared to the IP route. Results indicate that IP insulin causes a short lasting hypoglycaemia and consequently IP insulin increases food intake only after the 28th day of life.

Aging↗

[Regulation of milk intake in young ruminants].

We studied the influence of the three main nutritive components of milk - saccharides, fat and amino acids - on milk intake in suckling lambs and on the role of insulin as a key metabolic hormone for the regulation of milk intake. The intake was slowed down after p.o. administration of milk fat (p less than 0.05), after i. v. administration of methionine (p less than 0.001) and after p. o. administration of glucose, lactose (p less than 0.01, p less than 0.001) and sorbitol (p less than 0.001). After i. v. administration of glycerol, lysine, threonine, arginine, glucose, and i. v. and p. o. administration of galactose the intake of milk did not change significantly (p greater than 0.05). The findings indicate that the short-time regulation of milk intake in suckling ruminant animals is not subjected to the specific effect of some of the milk components. Regarding the metabolic effects, the problem concerns the speed of resorption of easily metabolizable sources of energy from the digestive system to the liver and to the whole body. Neutral Zn-insulin administered intraperitoneally at a dose of 4 U X kg-1 increased the milk intake (p less than 0.01, p less than 0.001), in 8 to 22 hours after the administration only when the animals were on the low-fat milk diet (5.9%-11% fat in dry matter). We assume that the long-range hyperphagy can be related mainly with the fast metabolizing of energy-rich substances (glucose) into the body stores (glycogen, fat) accompanied by subsequent hormonal changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Food intake control and RNA content of hypothalamic neurons in infant rats.

The influence of glycerol, glucose and lysine administration on the total RNA content in individual neurons of the ventromedial hypothalamus (VMH) and lateral hypothalamus area (LHA) in infant male rats was studied. Sixty minutes after administration, the total RNA content of the VMH neurons significantly decreased--from 13th day after glycerol and from 17th day after the glucose and lysine administration. The total RNA content of LHA neurons significantly increased from 17th day after glycerol and glucose and on 25th day after lysine administration. The noted changes of the RNA content, and especially the changes of the RNA proportion in these hypothalamic regions are well corresponding with the onset of the hypophagic effect of glycerol, glucose and amino acids in infant rats. The oppositional changes of the RNA content of VMH and LHA neurons are in conformity with the different role of these hypothalamic centers in food intake control.

Age Factors↗