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Biomedical subjects

B L Morgan

Publications and source records attributed to B L Morgan.

At least 19 recordsLinked to original sources

Intrachromosomal triplication of 2q11.2-q21 in a severely malformed infant: case report and review of triplications and their possible mechanism.

A female fetus with brain malformations, multicystic kidneys, absence of the right thumb, and a posterior cleft of palate was delivered at 32 weeks of gestation. Cytogenetic studies including FISH showed a novel intrachromosomal triplication of the proximal long arm of chromosome 2 (q11.2-q21), resulting in tetrasomy for this segment. The middle repeat was inverted. At least 11 patients with intrachromosomal triplications have been reported, mostly involving chromosome 15q. The mechanism involved in formation of these rearrangements is compatible with U-type exchange events among three chromatids.

Abnormalities, Multiple↗

Effects of hypothyroidism on the DNA, carbohydrate, soluble protein and sialic acid contents of rat submandibular glands.

Submandibular glands are a target organ of thyroid hormones. This study examined the effects of hypothyroidism on the biochemical characteristics of these glands in the rat. There were no effects on the neutral sugar and DNA contents. However, soluble protein concentrations (micrograms/mg wet weight) were significantly decreased and sialic acid concentrations micrograms/mg soluble protein) were significantly elevated.

Animals↗

The effect of alterations in ketone body availability on the utilization of beta-hydroxybutyrate by developing rat brain.

The effect of alterations in ketone body availability during the early postnatal period on the in vitro and in vivo utilization of beta-hydroxybutyrate (beta OHB) by developing rat brain was determined. Ketone body availability was prolonged by feeding a high fat diet during pregnancy and lactation and to pups after weaning. Availability was decreased by early weaning pups at 16 days to a low fat liquid diet. In the in vitro studies, oxidation of [14C]beta OHB to CO2 and incorporation into brain lipid was determined at 7, 14, 21, and 35 days of age. In the in vivo studies incorporation of [14C]beta OHB and [3H]glucose into brain lipid was measured. The results indicate that it is possible to alter the brain's utilization of beta OHB for lipid synthesis and energy metabolism during the developmental period. This was particularly evident in the in vivo studies. The in vivo results also suggest a relationship between beta OHB availability in the blood and incorporation into brain lipid. When availability was decreased by early weaning pups to the low fat diet, incorporation of beta OHB into lipid was also decreased. Likewise, when availability was increased, such as was seen in the high fat feeding study, incorporation was increased.

3-Hydroxybutyric Acid↗

Brain beta-hydroxybutyrate utilization in neonatal hypothyroidism in rats.

The in vitro and in vivo utilization of 14C-beta-hydroxybutyrate (BOHB) by the brain in neonatal hypothyroidism was studied in rat pups made hypothyroid by feeding dams a diet containing 0.02% propylthiouracil during pregnancy and lactation. In the in vitro studies, the oxidation of BOHB to CO2 was lower at 14 and 21 days of age in hypothyroid pups than in pair-fed controls but higher at 35 days. The incorporation of BOHB into brain lipid was significantly higher in hypothyroid pups at 14, 21 and 35 days. In contrast, in the in vivo studies, incorporation of BOHB into lipid was significantly lower in hypothyroid pups at 14 and 21 days. These results suggest that hypothyroid pups may have a normal or increased capability to use BOHB for lipid synthesis, but were unable to achieve normal rates of utilization in vivo, possibly due to a decreased substrate availability. These findings may have implications for the decreased brain lipid content characteristic of neonatal hypothyroidism.

3-Hydroxybutyric Acid↗

The effect of early postnatal undernutrition on the growth and development of the rat brain.

1. Rat pups were undernourished during the period of the brain growth-spurt by feeding their mothers a low-protein diet from the third day post partum. 2. The pups were killed on days 5, 6, 9, 12, 16, 20 and 24 post partum, and their brains were analysed for protein, DNA, glycosides and glycoproteins. The activities of four enzymes involved in neurotransmission, and in the synthesis of glycolipids and myelin were also measured. Results of the analyses were compared with those obtained for pups that were suckled by well-nourished dams. 3. The brains of the undernourished pups contained substantially less protein and DNA; gangliosides and glycoproteins were also reduced. 4. All four enzymes showed lower peak activities in the nutritionally deprived animals, and the attainment of peak activity was retarded by several days. 5. These results suggest that undernutrition imposed during the brain growth-spurt leads to a deficit in the glial cell population and thus in the capacity to form myelin, and reduced development of cellular processes.

Aging↗

A useful correlation between blood and brain N-acetylneuraminic acid contents.

A study was conducted to determine if serum N-acetylneuraminic acid (NeuAc) levels correlate with brain NeuAc levels. Sprague-Dawley rats were given either a diet containing 100 g casein/kg or one with 200 g casein/kg throughout pregnancy and lactation. At 12, 16 and 21 days' postpartum, litters of pups from each of the groups were killed. Their serum was assayed for NeuAc and their brains for total ganglioside and glycoprotein NeuAc. It was found that brain wet weight, ganglioside and glycoprotein NeuAc contents all correlate with serum NeuAc levels. It is suggested that serum NeuAc levels might represent a new method of measuring functional development of the brain.

Animals↗

Effects of essential fatty acid deficiency during late gestation on brain N-acetylneuraminic acid metabolism and behaviour in the progeny.

1. Rat dams given a diet containing 100 g maize oil/kg for approximately two weeks before mating and during the first 14 d of gestation, were given the same diet or one containing 100 g hydrogenated coconut oil/kg (essential fatty acid (EFA)-deficient) in place of maize oil until parturition. After parturition the dams were given the same diets and all progeny were weaned to the maize oil diet at 21 d of age. Brain N-acetylneuraminic acid (NeuNAc) content as well as neuraminidase (sialidase; (EC 3.2.1.18), and cytidine monophosphate N-acetylneuraminic acid synthetase (CMP-NeuNAc synthetase) activities were measured at days, 7, 14, 21 and 168 in the progeny. Y-maze learning was measured at 168 d. 2. Brain weight was independent of dietary fat at all ages. 3. Lack of EFA in the maternal diet during gestation and lactation depressed ganglioside and glycoprotein NeuNAc levels and the activities of sialidase and CMP-NeuNAc synthetase. 4. Maternal dietary deprivation of EFA irreversibly impaired learning behaviour of the progeny. A relationship exists between early exposure to EFA deficiency and learning potential of the progeny.

Animals↗

The subcellular localization of administered N-acetylneuraminic acid in the brains of well-fed and protein restricted rats.

1. This study investigated the subcellular localization of injected N-acetylneuraminic acid (NeuNAc) in brain. Forty pregnant rats were distributed into four groups. Two groups were given a 200 g casein/kg diet and the other two groups a 100 g casein/kg diet throughout gestation. One group from each of the low- and high-protein groups were given their respective diets for the first 11 d of lactation. On day 12 of lactation, 2.5 microCi [14]NeuNAc/kg body-weight were injected intraperitoneally into their pups. After 1 h the pups were killed, their brains removed and subjected to subcellular fractionation. On day 16 of lactation the other two groups were similarly treated. 2. In all groups of animals 80% of the [14C]NeuNAc incorporated into the brains was found in the synaptosomal fraction and the remainder distributed among the other subcellular fractions in proportion to their total NeuNAc content. 3. These results suggest that NeuNAc exerts its effects on behaviour via the synaptic membrane.

Animals↗

Effects of administration of N-acetylneuraminic acid (NANA) on brain NANA content and behavior.

Rat pups were malnourished during the first 3 weeks after birth. Experimental rats were injected intraperitoneally with 1 mg N-acetylneuraminic acid (NANA) per 50 g body weight daily from 14 to 21 days postnatally. Control animals were similarly injected with 1 mg glucose per 50 g body weight. At 21 days of age, the rats were tested in an open field and their brains analyzed for protein, DNA, ganglioside NANA and glycoprotein NANA. The administration of NANA was associated with an increase in cerebral and cerebellar ganglioside and glycoprotein NANA concentrations. However, it had no effects on brain weight, cell size and number. There was also a reduction in the expected behavioral abnormalities secondary to malnutrition. At 21 days of age, similarly treated littermates of the experimental animals were weaned to a stock diet and tested in a Y maze at 6 months of age. Rats treated with NANA learned the maze quicker than controls and the previously noted changes in brain biochemistry were found to have persisted. Intraperitoneal injection of [14C]NANA into malnourished rats during the same period showed that it was readily incorporated into brain glycoproteins and gangliosides. The possibility that the brain concentration of NANA has an effect on behavior is discussed.

Animals↗

Effects of environmental stimulation on brain N-acetylneuraminic acid content and behavior.

A study was conducted in which the nutritional and early stimulation conditions of rat pups were manipulated during the first 3 weeks of life. Early stimulation reduced the change in open-field behavior caused by malnutrition at 21 days postnatally. The cerebrum and cerebellum were analyzed for ganglioside and glycoprotein N-acetylneuraminic acid (NANA), DNA and protein content. The improved behavioral performance was associated with a significantly higher ganglioside and glycoprotein NANA content in both brain areas analyzed. The remaining rats from each litter were weaned onto a standard laboratory stock diet at 21 days of age and housed individually until age 6 months. At this time, their performance in a Y maze was tested. Once again early stimulation was associated with an improved ability to learn the maze. The biochemical changes persisted into adulthood in the stimulated groups with the exception that the difference in cerebellar ganglioside content had disappeared by this time. The results are discussed with respect to the possible role of NANA in behavior.

Aging↗

Value of dietary protein for hyperplastic growth at restricted energy intakes.

The study describes three experiments of similar design relating dietary protein to growth over a period of 16 days in rats prematurely weaned at 19 days of age. In experiment 1, group 1 was fed ad libitum a 10% caseindiet. Group 2 was pair-fed an isoenergetic 40% casein diet. Groups 3 and 4 received 3 g of the 10% casein and 40% casein diets, respectively. The experiment demonstrated that protein may be used to sustain growth when energy intake is restricted. In experiment 2, all rats were given 3 g of diet per day. Group 1 was given the 10% casein diet, group 2 the 40% casein diet, group 3 a diet with 10% casein plus 30% of a mixture of dispensable amino acids and group 4 the 10% casein diet plus an energy supplement. Results showed that amino nitrogen seems to be a requisite for organ protein synthesis. In experiment 3, group 1 ate the 10% casein diet, group 2 the amino acid-supplemented diet and group 3 the latter minus glycine. Group 3 showed increased liver and kidney growth. The inclusion of glycine in group 2 caused a further increment in organ protein content.

Animals↗

The effects of folic acid supplementation during pregnancy in the rat.

1. Twenty-four Sprague-Dawley female rats were randomly assigned to three groups (groups A, B, C). Group A was given a folic acid-free diet and groups B and C received 0.0018 g folic acid/kg diet. Rats in group C were also given a supplement of 1 mg folic acid/d by intraperitoneal injection. 2. After 14 d of feeding the rats were mated. The diets were continued throughout gestation. On day 21, of gestation the dams were killed and their livers and products of conception assayed for RNA, DNA, protein and tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate dehydrogenase; EC 1.5.1.3) activity. 3. The foetuses, placentas and livers from supplemented rats (group C) were significantly larger than those from groups A and B and had a higher content of RNA, DNA and protein. Those tissues from group A dams were smaller than those from the other groups and had a correspondingly reduced nucleic acid and protein content. 4. The activity of tetrahydrofolate dehydrogenase, the first and rate-limiting enzyme in the metabolism of folate, was increased in the folate supplemented rats (group C) and reduced in the rats given a folic acid-free diet (group A). These changes in enzyme activity could explain the differences in nucleic acid biosynthesis and growth shown by the different groups.

Animals↗

Effects on the products of conception of protein supplementation of the diets of rats.

Pregnant rats were ad libitum fed diets of varying casein content from conception. The food intake was measured. The control rats the first 17 days of gestation and 25% casein plus 2.5% DL methionine during the remainder; the second experimental group was given the 25% casein plus 2.5% DL methionine throughout pregnancy. Maternal food intakes were little changed by the supplement, but the rats in the second experimental group ate considerably more. The dietary regimens of the experimental groups had no effect on lean body mass, but did significantly increase carcass fat content. A protein supplement given in late pregnancy, at the time of the fetal exponential growth phase, was found to increase the weight, protein content and cellularity of fetal brains and carcasses. It also increased the weight and protein content of placentas, but had no effect on their cellularity.

Animals↗

Effects of malnutrition on some aspects of RNA metabolism in the maternal liver and fetal tissues at different stages of pregnancy in the rat.

A comparison was made between rats fed diets containing either 5% casein or 25% casein, both being supplemented with DL-methionine, from the first day of pregnancy. Livers of dams killed on days 7, 14, and 21 and whole fetuses on days 12, 14, and 21 were weighed, analyzed for protein, RNA and DNA content and assayed for ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (SAMD). Free and total alkaline ribonuclease activity were also measured in the maternal livers. Malnutrition reduced the characteristic increase in content of DNA, RNA and protein in the maternal liver and fetus. In control rats total hepatic RNase activity increased and free RNase activity decreased during late pregnancy. In the deprived group, total activity decreased and free activity increased during late pregnancy. Liver and fetal ODC and SAMD activities were reduced by undernutrition. These studies show that malnutrition reduced both growth and the accretion of RNA in livers and fetuses of rat dams. These changes coincide with a reduced activity of polyamine synthesizing enzymes suggesting that there is a functional relationship between polyamines and RNA. High hepatic free RNase activity in malnourished dams may help to limit any build up in RNA content.

Adenosylmethionine Decarboxylase↗