PubMed Health⌕ Search

Biomedical subjects

G J Anderson

Publications and source records attributed to G J Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and spectroscopy of membrane receptor proteins. The gamma subunit of the IgE receptor.

The high-affinity receptor for IgE is a tetrameric complex of subunits of the type alpha beta gamma 2. We report here conformational studies of the intact gamma subunit in trifluoroethanol and water/liposomes by circular dichroism and Fourier-transform infrared (FTIR) spectroscopy. In trifluoroethanol, the FTIR amide I' frequencies were consistent with two predominant conformational components, the beta-turn and alpha-helix, whilst in liposomes consisting of D2O and dimyristoylglycerophosphocholine (Myr2GroPCho), three components were observed. The third component present may contain some left-handed extended helix. Spectral simulation was carried out to demonstrate that the CD spectra were consistent with the component conformations identified from FTIR spectroscopy. The stimulated CD spectra were in excellent agreement with the experimental spectra. The intact gamma subunit conformation in trifluoroethanol was shown to possess 72% alpha-helical and 28% beta-turn conformations. In water/Myr2GroPCho liposomes the percentage of each conformational component present is 37%, 38% and 25% for the alpha-helix, beta-turn and extended structures, respectively. Assuming that the transmembrane fragment was alpha-helical, an excellent correlation was found between this derived alpha-helical content in water/liposomes (37%) and from hydrophobicity plots where the percentage of amino acids in the transmembrane domain is predicted by others to be 34%. It is suggested that the beta-turn detected by CD and FTIR was attributable to a 3(10) helix rather than a type I or type III reverse turn.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1992

Reversibility of the effects of dietary fish oil on the fatty acid composition of the brain and retina of growing chicks.

Dietary fish oil increases levels of (n-3) fatty acids in the brain and retina of younger animals but has less effect in adults. The duration of the effects of fish oil in young animals, as well as the extent of reversibility of the effects, are unknown. Laying hens were fed either a fish oil diet or a soybean oil-based control diet. Resulting chicks were assigned to three diet groups: chicks from fish oil and soybean oil hens were continued on fish oil and soybean oil diets, respectively, for 0, 3, 6, or 9 weeks, and additional chicks from the fish oil hens were fed the fish oil diet for 0, 3, or 6 weeks and then reversed to the soybean oil diet for a period of 3 weeks. The fatty acid composition of the brain, retina, liver, and serum of the reversal chicks was compared with chicks fed the fish oil diet only or the soybean oil diet only. Brain levels of docosahexaenoic acid (22:6(n-3)) decreased substantially when reversal from the fish oil diet to the control diet was begun at hatching, but did not decrease when reversal was begun at later times. Other (n-3) fatty acids in the brain, docosapentaenoic acid (22:5(n-3)) and eicosapentaenoic acid (20:5(n-3)), decreased substantially at all ages, and to a greater extent than 22:6(n-3). Brain arachidonic acid (20:4(n-6)), which was low in fish oil chicks, rose to control after reversal at hatching, but recovered only partially when reversal was begun at later times. A similar patterns was observed in the retina. Serum and liver (n-3) fatty acids fell to control in all reversal chicks, and (n-6) fatty acids increased to control, except in chicks reversed at 6 weeks. This study demonstrates that by 3 weeks of age the chick brain strongly resists diet-induced lowering of high levels of 22:6(n-3).

Analysis of Variance↗
PubMed1992

Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron.

The principal iron uptake system of Saccharomyces cerevisiae utilizes a reductase activity that acts on ferric iron chelates external to the cell. The FRE1 gene product is required for this activity. The deduced amino acid sequence of the FRE1 protein exhibits hydrophobic regions compatible with transmembrane domains and has significant similarity to the sequence of the plasma membrane cytochrome b558 (the X-CGD protein), a critical component of a human phagocyte oxidoreductase, suggesting that FRE1 is a structural component of the yeast ferric reductase. FRE1 mRNA levels are repressed by iron. Fusion of 977 base pairs of FRE1 DNA upstream from the translation start site of an Escherichia coli lacZ reporter gene confers iron-dependent regulation on expression of beta-galactosidase in yeast. An 85-base-pair segment of FRE1 5' noncoding sequence contains a RAP1 binding site and a repeated sequence, TTTTTGCTCAYC; this segment is sufficient to confer iron-repressible transcriptional activity on heterologous downstream promoter elements.

Amino Acid Sequence↗
PubMed1992

Lipidic peptides. V: Penicillin and cephalosporin acid conjugates with increased lipophilic character.

Lipophilic, double-ester derivatives of beta-lactam antibiotics with methylene, ethylene, and propylene spacers were prepared by crown-ether-assisted coupling of halogenoalkyl esters of 2-(tert-butoxycarbonylamino)decanoic acid to either penicillin G or cefuroxime. The hydroxyethyl ester of penicillin G and the tert-butoxypropyl ester of cefuroxime were also prepared. The lipophilic, double-ester conjugates, the hydroxyethyl ester of penicillin G, and the tert-butoxypropyl ester of cefuroxime showed weak or no antibiotic activity in vitro, as expected. The lipophilic penicillin G conjugates and the tert-butoxypropyl ester of cefuroxime were active in vivo against a nonpenicillinase-producing strain of Staphylococcus aureus after subcutaneous administration. The penicillin G double ester with propylene spacer and the tert-butoxypropyl ester of cefuroxime were inactive in vitro, a fact indicating that both compounds were hydrolyzed in vivo, as desired. After oral administration, the lipophilic, double-ester conjugate of penicillin G with methylene spacer and the tert-butoxypropyl ester of cefuroxime were active.

Administration, Oral↗
PubMed1992

Nasopharyngeal malignancies in children.

A retrospective analysis identified 29 children with nasopharyngeal malignancies who were evaluated at the Children's Hospital of Philadelphia from 1970 through 1989. Rhabdomyosarcoma (15) and carcinoma (9) were the most common tumor types, and there were distinct differences in the clinical presentations of these two malignancies. Patients with rhabdomyosarcoma were generally younger than those with carcinoma and enjoyed longer survival. Six (67%) of the children with carcinoma were black; all of the patients with rhabdomyosarcoma were white. Patients with carcinoma were also more likely to present with cervical metastases. The presentation, evaluation, and methods of treatment for pediatric nasopharyngeal malignancies are discussed.

Adolescent↗
PubMed1991

High levels of the (n-6) fatty acid 4,7,10,13,16-docosapentaenoate in the retinas of rabbits are reduced by feeding dietary fish oil from birth to adult life.

High levels of 4,7,10,13,16-docosapentaenoic acid [22:5(n-6)], a fatty acid usually associated with (n-3) fatty acid deficiency, have been reported in the retina of young rabbits. We studied the fatty acid composition of the rabbit retina throughout development, from birth to adult life. We also attempted to modify the fatty acid composition of the retina by the feeding of fish oil, high in docosahexaenoic acid [22:6(n-3), DHA]. Female rabbits were fed either a control or 2% fish oil diet through pregnancy and the nursing period. Weaned rabbits received the mothers' diet. In the retinas of control rabbits, 22:5(n-6) represented 3.7% of total fatty acids at birth, reached 15.1% at 9 wk and declined to 5.6% in adult rabbits. However, 22:6(n-3) increased steadily from birth onwards, from 3.8% of total fatty acids at birth to 19.6% in adults. Dietary fish oil increased the trace concentrations of long-chain (n-3) fatty acids in the milk to 10% of total fatty acids, reduced retinal 22:5(n-6) to less than or equal to 0.5% at all ages, and increased DHA to approximately 30% by 9 wk. Retinal phosphatidylethanolamine was even more sensitive to the impact of the fish oil diet, with DHA levels in newborn rabbits rising from 10% (control diet) to 43% of total fatty acids. These results demonstrated that 22:5(n-6) in the normal rabbit retina remains elevated (compared with other species) at all ages even as retinal DHA increases. The great increase of DHA in newborns whose mothers were fed fish oil suggests placental transfer of DHA and incorporation into retinal lipids.

Animals↗
PubMed1991

Intestinal transferrin receptors and iron absorption in the neonatal rat.

The transferrin receptor is a major protein found on the basolateral membranes of intestinal epithelial cells, yet its possible role in intestinal iron metabolism and also in iron absorption is unclear. We have studied intestinal transferrin receptor expression during the peri- and postnatal development of the small intestine of the rat using immunohistochemistry with a monoclonal antibody to the rat receptor. Two major changes in transferrin receptor expression in the developing small intestine were found, a decrease in receptor expression associated with birth, and an increase at the time of weaning. Around the time of weaning there was a large decrease in iron absorption, but there was no direct correlation between absorption and transferrin receptor expression. However, at both birth and weaning there were major changes in intestinal cell kinetics, and the distribution of receptor correlated well with the distribution of proliferating cell populations. In addition, as the intestinal epithelial cells differentiated and stopped dividing, there was a redistribution of transferrin receptors from the cell surface to intracellular sites. These data suggest that the most likely role of the transferrin receptor in the neonatal intestine is in the supply of iron to the developing epithelial cells in the crypts, and that the receptor does not play a direct role in iron transit across the intestinal epithelium.

Aging↗
PubMed1991

The incorporation of n-3 and n-6 essential fatty acids into the chick embryo from egg yolks having vastly different fatty acid compositions.

The effect of egg yolk fatty acid composition on essential fatty acid utilization by the developing chick embryo was studied by feeding laying hens a fat-free diet supplemented with oils containing widely divergent contents of the essential n-6 and n-3 fatty acids. A control hen was fed a commercial feed for laying hens. The diets contained 20 to 4370 mg/100 g n-3 fatty acids and 360 to 8020 mg/100 g n-6 fatty acids. Fertile eggs were collected in pairs: one was incubated and the other served as an unincubated control. The fatty acid content of the unincubated egg and the newly hatched chick from each pair was compared. Some 50% of the total fatty acids in the egg yolk were incorporated into the tissues of the newly hatched chick. Regardless of diet, more yolk n-6 fatty acids were incorporated into the chick compared to saturated or monounsaturated fatty acids. The percentage of incorporation especially increased from the eggs containing relatively low amounts of n-6 fatty acid. The percentage of incorporation of n-3 fatty acids was similar to that of saturated and monounsaturated fatty acids when n-3 fatty acids were plentiful in the egg yolk, but increased significantly when n-3 fatty acids were low in the eggs. There was a generally linear relationship between essential fatty acids in the egg and in the chick, although levels of docosahexaenoic acid [DHA; 22:6(n-3)] in the brain did not respond proportionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

A nuclear translational block imposed by the HIV-1 U3 region is relieved by the Tat-TAR interaction.

Replication of HIV-1 depends on the viral Tat protein, which functions via a target sequence, TAR, present in the proviral long terminal repeat (LTR) and at the 5' end of viral mRNAs. We have shown that Tat potentiates the expression of TAR-containing RNAs, but only when Tat and the TAR-containing RNA are present in the nucleus. We now show that a small change in the TAR loop abolishes nuclear potentiation by Tat. Furthermore, the HIV-1 U3 region induces expression incompetence in mRNA synthesized by this promoter. RNAs of identical structure are, however, translated efficiently when produced from the CMV-IE promoter. The Tat-TAR system appears, therefore, to rescue the expression potential of HIV-1 LTR-directed RNA.

Animals↗
PubMed1990

Rhabdomyosarcoma of the head and neck in children.

Rhabdomyosarcoma is the most common soft-tissue sarcoma in infants and children, with the head and neck being the most frequent site of involvement. Treatment for this neoplasm has undergone many changes, with a much improved prognosis using a combination of surgery, radiation therapy, and chemotherapy. This retrospective analysis presents the management and outcome of 60 children (aged 3 months to 18 years) with rhabdomyosarcoma of the head and neck evaluated at the Children's Hospital of Philadelphia (Pa) between 1970 and 1987. The overall death rate for all head and neck sites decreased from 50% in 1970 to 1979 to 23% in 1980 to 1987, reflecting the improved management protocol.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Transferrin receptor distribution and regulation in the rat small intestine. Effect of iron stores and erythropoiesis.

A combination of biochemical quantitation and immunohistochemistry has been used to examine in detail transferrin receptor distribution and expression in the rat small intestine and its relationship to iron absorption. Receptor numbers were quantitated by transferrin binding to preparations of basolateral or brush-border membranes. Receptors were demonstrated on the basolateral membranes of the gut cells, but not on the brush-border fraction. Apotransferrin demonstrated little binding to basolateral membranes at physiological pH. Dietary or parenteral iron loading of animals produced a significant decline in transferrin binding, whereas binding was increased in iron deficiency. These data were confirmed by immunohistochemical studies using a monoclonal antibody to the transferrin receptor. When iron absorption was increased threefold following acute hemolysis and without a decrease in body iron stores, there was no change in transferrin receptor number. These data indicate that intestinal transferrin receptors may be regulated by body iron stores but suggest that they are not directly involved in iron absorption.

Absorption↗
PubMed1990

Placental transfer of essential fatty acids in humans: venous-arterial difference for docosahexaenoic acid in fetal umbilical erythrocytes.

Docosahexaenoic acid [22:6(n-3); 22:6(4,-7,10,13,16,19) (DHA)] is required in quantity by the developing nervous system of the fetus. This need could be met through synthesis of DHA from linolenic acid in the fetus or through placental transfer of DHA directly. To study the placental transfer of n-3 fatty acids, we obtained umbilical and maternal blood samples from 26 healthy women and infants at parturition and measured the fatty acid composition and content of both plasma and erythrocytes. A striking finding was a considerable venous-arterial difference for DHA in the umbilical erythrocytes as a proportion of total fatty acids and in absolute concentration. This difference of 2.2 micrograms per billion erythrocytes was 6 times larger than the difference in fetal plasma, when the plasma and erythrocyte concentrations were normalized to whole blood. Most other erythrocyte fatty acids showed a similar trend. In umbilical plasma, significant venous-arterial differences were found for 16:0, 16:1, 18:2, and total saturated fatty acids. There was a similar trend for most other plasma fatty acids. Compared with maternal blood, fetal plasma and erythrocytes had higher levels of 20:4 and DHA and lower levels of 18:2 and 18:3(n - 3) fatty acids as a proportion of total fatty acids. These results suggest that erythrocytes play a major role in the necessary transport of the essential fatty acid DHA into the fetus.

Arachidonic Acid↗
PubMed1990

A mammalian protein of 220 kDa binds pre-mRNAs in the spliceosome: a potential homologue of the yeast PRP8 protein.

A mammalian protein of approximately 220 kDa (p220) was UV-crosslinked to precursor mRNAs (pre-mRNAs) under splicing conditions. The kinetics and biochemical requirements of the UV-crosslinking of p220 corresponded to the kinetics and biochemical requirements of spliceosome formation. On Western blots, antibodies against the yeast splicing factor PRP8 recognized a doublet of proteins, the faster migrating of which comigrated with p220. Furthermore, UV-crosslinked p220 was immunoprecipitated with anti-PRP8 antisera. These results suggest structural conservation of the splicing factor PRP8 from yeast to mammals and show that this protein is in close proximity to the pre-mRNA in the spliceosome.

Blotting, Western↗
PubMed1990

Effects of dietary n-3 fatty acids on the phospholipid molecular species of monkey brain.

We examined the changes in the molecular species of brain ethanolamine glycerophospholipids of monkeys fed diets containing widely ranging amounts of n-3 fatty acids. Two groups of rhesus monkeys were fed pre- and postnatally either a control diet (soy oil; containing 8% of fatty acids as 18:3n-3) or a deficient diet (safflower oil; containing less than 0.3% 18:3n-3). The brains of these animals were analyzed at 22 months of age. A third group of monkeys was fed the safflower oil diet to 22 months of age and then switched to a fish oil diet (28% long-chain n-3 fatty acids) for 1-2 years before autopsy. The molecular species of the diacyl, alkylacyl, and alkenylacyl ethanolamine glycerophospholipids from frontal cortex were separated by HPLC. A total of 24 molecular species were identified. Fatty acids in the sn-2 position differed markedly among the diet groups, but the sn-1 position always contained only 16:0, 18:0, or 18:1. In the diacyl subclass of the control brain, the n-3 molecular species represented 41% of total and the n-6 species 45%, whereas in the deficient brain the n-3 molecular species decreased to 9% and n-6 molecular species increased to 77%. The fatty acid 22:5n-6 did not replace 22:6n-3 in a symmetrical fashion in the molecular species of the deficient brain. In the brains of the fish oil-fed monkeys, the n-3 molecular species amounted to 61% and n-6 molecular species were reduced to 25%. The species 18:1-22:6, 16:0-22:6, and 18:0-22:6 generally changed proportionally in response to diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Docosahexaenoic acid is the preferred dietary n-3 fatty acid for the development of the brain and retina.

The metabolism of individual dietary n-3 fatty acids was studied in n-3 fatty acid-deficient newly hatched chicks. Laying hens were fed the n-6 fatty acid, ethyl linoleate, as the only source of polyunsaturated fat. Chicks were then fed the n-3-deficient hens' diet, or one of three other diets supplemented with the ethyl ester of 18:3 n-3, 20:5 n-3 [eicosapentaenoic acid (EPA)], or 22:6 n-3 [docosahexaenoic acid (DHA)] at 0.44% of calories. At the end of 0, 1, 2, and 3 wk, the fatty acid composition of the brain, retina, liver, and serum was determined. Dietary EPA and DHA were equally effective at raising levels of DHA in the brain and retina. Dietary 18:3 was relatively ineffective in restoring brain and retina DHA. In the n-3-deficient chicks fed EPA or DHA, levels of DHA recovered to control values in both the brain and retina by 3 wk. Very little EPA accumulated in the brain or retina of chicks fed EPA. Hepatic synthesis of DHA from EPA appeared low, suggesting that the brain and retina synthesized the DHA that accumulated rapidly in these tissues after the feeding of EPA. The delta-4-desaturase enzyme was apparently very active, then, in the brain and retina. Retroconversion of dietary 22:6 to 22:5 and 20:5 was evident in the serum, liver, and retina but not in the brain. Thus, it was possible to study the relative metabolism and especially the interconversion of n-3 fatty acids in a environment uncomplicated by existing stores of these essential fatty acids. This study would suggest that 18:3 as the sole source of n-3 fatty acids in the diets of animals, including the human infant, may not be adequate for the biochemical development of the brain and retina and that dietary DHA is the preferred fatty acid of the n-3 series.

Animals↗