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L Morgan

Publications and source records attributed to L Morgan.

At least 19 recordsLinked to original sources
PubMed1992

Switch recombination breakpoints are strictly correlated with DNA recognition motifs for immunoglobulin S gamma 3 DNA-binding proteins.

The deletion looping out model of switch (S) recombination predicts that the intervening DNA between switch regions will be excised as a circle. Circular excision products of immunoglobulin switch recombination have been recently isolated from lipopolysaccharide (LPS)-stimulated spleen cells. The recombination breakpoints in these large circles were found to fall within switch regions. Since switch recombination is clearly focused on switch regions, we hypothesized that some DNA-binding protein factor might be involved in specifically recognizing and facilitating the alignment of switch regions before recombination. Two DNA-binding proteins that specifically interact with two discrete regions of the S gamma 3 tandem repeat have been identified in crude and partially purified nuclear extracts derived from LPS- and dextran sulfate (DxS)-activated splenic B cells. The first factor has been found indistinguishable from NF-kappa B by mobility shift assays, methylation interference, competition binding studies, and supershift analysis using an antiserum specific for the p50 component. The second appears to be composed of two closely traveling mobilities that do not separate upon partial purification. This second complex is unique and specific for S gamma 3 by methylation interference assays and competition-binding analysis. The sites at which recombination occurs in the S gamma 3 switch region have been analyzed and found to strictly correlate with the binding sites of the S gamma 3 switch binding proteins.

Amino Acid Sequence↗
PubMed1992

Effects of n-3 fatty acids on postprandial triacylglycerol and hormone concentrations in normal subjects.

The present study reports results from two investigations to determine effects of a 6-week period of moderate n-3 fatty acid supplementation (2.7 g/d) on fasting and on postprandial triacylglycerol and metabolic hormone concentrations in response to standard test meals. In the first study postprandial responses were followed for 210 min after an early morning test meal challenge; in the second study responses to an evening test meal were followed during the evening and overnight for a total period of 12 h. In both studies postprandial triacylglycerol responses to the test meals were significantly reduced after compared with before fish-oil supplementation. In the second study the triacylglycerol peak response seen between 200 and 400 min in subjects studied before supplementation with fish oils was almost completely absent in the same subjects after 6 weeks of n-3 fatty acid supplementation. Analysis of fasting concentrations of metabolites and hormones was carried out on the combined data from the two studies. There were no significant differences in total, low-density-lipoprotein- or high-density-lipoprotein-cholesterol concentrations during fish-oil supplementation, although there was considerable individual variation in cholesterol responses to the supplement. Concentrations of Apo-B and Apo-A1 were unchanged during supplementation with fish oils. Fasting and early morning postprandial GIP concentrations were lower in subjects taking fish oils, possibly due to acute effects of fish-oil capsules taken on the evening before the studies. In both studies fasting insulin and glucose and postprandial insulin concentrations remained unchanged following fish-oil supplementation. The results do not support the view that triacylglycerol-lowering effects of n-3 fatty acids are due to modulation of insulin secretion mediated via the enteroinsular axis. Further studies are required to determine the precise mechanism by which fish oils reduce both fasting and postprandial triacylglycerol concentrations.

Adult↗
PubMed1992

The use of antisense mRNA to inhibit the tonoplast H+ ATPase in carrot.

Carrot root cells were transformed with the coding or 5' noncoding regions of the carrot vacuolar H+ ATPase A subunit cDNA cloned in the antisense orientation behind the cauliflower mosaic virus 35S promoter. Bafilomycin-sensitive ATPase, H(+)-pumping, and 14C-O-methyl-glucose uptake activities were specifically inhibited in the tonoplast fractions of mutant cell lines. Protein gel blotting confirmed that the expression of the A subunit was inhibited in the tonoplast fraction, but not in the Golgi fraction. Two-dimensional protein gel blots of total microsomes of wild-type and control transformant cell lines revealed two major immunoreactive polypeptides in the acidic pI range. In contrast, highly purified tonoplast membranes contained only the less acidic polypeptide. Because the less acidic polypeptide was preferentially diminished in the two antisense cell lines, we infer that the antisense constructs specifically blocked expression of a tonoplast-specific isoform of the V-ATPase A subunit in carrot. Regenerated plants containing the antisense constructs exhibited altered leaf morphologies and reduced cell expansion. The altered phenotype was correlated with the presence of the antisense construct.

Base Sequence↗
PubMed1991

Specific growth factor activity identifies and predicts murine mammary tumor.

In milk from substrains of mice with varying incidences of developing mammary tumor, we have isolated a specific mitogenic activity, which is unique in that it identifies mice with mammary tumor and predicts those mice that will eventually develop mammary tumor. None of the milk samples from control mice, who never developed mammary tumor, contained this specific predictive mitogenic activity. Chemical characterization has shown this specific mitogenic activity to be acid- and heat-stable and resistant to reducing agents. Partial purification, by ion-exchange, high-performance liquid chromatography size-exclusion, and isoelectrofocusing techniques, of this specific mitogenic activity from milk of mice that had or eventually developed mammary tumor identifies several peptide growth factor components in a 6-10 kDa molecular weight range. Of known growth factors, radioassay techniques identify an insulin-like growth factor-1-like peptide as a major component. Small amounts of platelet-derived growth factor and transforming growth factor-beta activities also were present. Our results suggest that a subset of growth factors that are diagnostic of the presence of murine mammary tumor and predictive of eventual tumor development may be early indicators of the transition of a competent cell to a progressively malignant state. Similar studies of a secreted body fluid from women at risk for breast cancer may lead to the identification of a specific biologic tumor marker for breast cancer.

Animals↗
PubMed1991

The effects of cAMP on differentiation of cultured Schwann cells: progression from an early phenotype (04+) to a myelin phenotype (P0+, GFAP-, N-CAM-, NGF-receptor-) depends on growth inhibition.

The present experiments were designed to clarify the relationship between cAMP elevation, proliferation and differentiation in Schwann cells. They were carried out on short-term cultures of cells obtained from neonatal rat sciatic nerves. It was found that the myelin-related phenotype was expressed in response to agents that elevate or mimic intracellular cAMP (forskolin, cholera toxin, cAMP analogues), provided cell division was absent. This phenotype included upregulation of the major myelin protein P0 and downregulation of GFAP, N-CAM, A5E3, and NGF receptor. In contrast, when cells were cultured in conditions where cell division occurred, elevation of intracellular cAMP produced an alternative response, characterized by DNA synthesis and absence of myelin-related differentiation. The cAMP mediated induction of an early Schwann cell antigen, 04, followed a different pattern since it was induced equally in dividing and nondividing cells. These observations are consistent with the proposal that during development of the rat sciatic nerve: (a) cAMP elevation, possibly induced by axon-associated factors, is a primary signal responsible for the induction of 04 expression in proliferating Schwann cells during the premyelination period; (b) subsequent withdrawal of cells associated with the larger axons from the cell cycle acts as a permissive secondary signal for induction of myelination, since in quiescent cells the ongoing cAMP elevation will trigger myelination.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7-36) amide, on fatty acid synthesis in explants of rat adipose tissue.

The effect of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1(7-36) amide, (GLP-1(7-36) amide), glucagon-like peptide-2 (GLP-2), glucagon and insulin on fatty acid synthesis in explants of rat adipose tissue from various sites was investigated. GIP, GLP-1(7-36) amide and insulin stimulated fatty acid synthesis, as determined by measuring the incorporation of [14C]acetate into saponifiable fat, in a dose-dependent manner, over the concentration range 5-15 ng/ml (0.87-2.61 nmol/l) for insulin and 0.5-7.5 ng/ml for GIP (0.10-1.50 nmol/l) and GLP-1(7-36) amide (0.15-2.27 nmol/l). Insulin and GIP caused a significantly greater stimulation of [14C]acetate incorporation into fatty acids in omental adipose tissue than in either epididymal or subcutaneous adipose tissue. Both GIP and GLP-1(7-36) amide had the ability to stimulate fatty acid synthesis within the physiological range of the circulating hormones. At lower concentrations of the hormones, GLP-1(7-36) amide was a more potent stimulator of fatty acid synthesis than GIP in omental adipose tissue culture; the basal rate of fatty acid synthesis was 0.41 +/- 0.03 pmol acetate incorporated/mg wet weight tissue per 2 h; at 0.10 nmol hormone/1 1.15 +/- 0.10 and 3.40 +/- 0.12 pmol acetate incorporated/mg wet weight tissue per 2 h for GIP and GLP-1(7-36) amide respectively (P less than 0.01). GLP-2 and glucagon were without effect on fatty acid synthesis in omental adipose tissue. The study indicates that GIP and GLP-1(7-36)amide, in addition to stimulating insulin secretion, may play a direct physiological role in vivo, in common with insulin, in promoting fatty acid synthesis in adipose tissue.

Adipose Tissue↗
PubMed1991

Five-year follow-up of rural Jamaican children whose mothers used marijuana during pregnancy.

This research provides data on the development of 59 Jamaican children, from birth to age 5 years, whose mothers used marijuana during pregnancy. Approximately one-half of the sample used marijuana during pregnancy and were matched with non-users according to age, parity, and socioeconomic status. Testing of the children was done at 1, 3, and 30 days of age with the Brazelton Neonatal Behavioral Assessment Scales and at ages 4 and 5 years with the McCarthy Scales of Children's Abilities. Data about the child's home environment and temperament were collected from direct observations as well as from standardized questionnaires. The results show no significant differences in developmental testing outcomes between children of marijuana-using and non-using mothers except at 30 days of age when the babies of users had more favourable scores on two clusters of the Brazelton Scales: autonomic stability and reflexes. The developmental scores at ages 4 and 5 years were significantly correlated to certain aspects of the home environment and to regularity of basic school (preschool) attendance.

Adult↗
PubMed1990

An mRNA from human brain encodes an isoform of the B subunit of the vacuolar H(+)-ATPase.

The B subunit (approximately 60 kDa) of the vacuolar H(+)-ATPase is one of the two major subunits comprising the hydrophilic catalytic complex of the enzyme. Using left and catalytic complex of the enzyme. Using left and right primers which bind two highly conserved sequences of the B subunit, an 836-base pair fragment was amplified from human brain cDNA by the polymerase chain reaction. The amplified fragment was used to probe a Northern blot and to screen a brain cDNA library. A single RNA band, 3.2 kilobases (kb) in length, was detected on Northern blots. A positive cDNA clone containing a 2.5-kb insert was isolated and sequenced. It included a long 3'-untranslated region (greater than 1.2 kb) and was missing a minor portion of the 5'-end of the coding region. The coding region of the brain cDNA sequence was 77% identical at the nucleotide level and 90% identical at the amino acid level to the previously reported sequence for the B subunit of the vacuolar H(+)-ATPase from human kidney (Sudhof, T. C., Fried, V. A., Stone, D. K., Johnston, P. A., and Xie, X.-S. (1989) Proc. Natl. Acad. Sci, U. S. A. 86, 6067-6071). Within the coding region of the brain cDNA, which is 6 amino acid residues shorter at the 3'-end than the kidney sequence, an 11% difference in the GC content was calculated. The 3'-noncoding sequence of the brain cDNA was completely unrelated to that of kidney and was three times longer. We conclude that the B subunit cDNAs from human kidney and brain represent different isoforms. This is the first demonstration of an isoform of a vacuolar H(+)-ATPase subunit.

Aged↗
PubMed1990

04 and A007-sulfatide antibodies bind to embryonic Schwann cells prior to the appearance of galactocerebroside; regulation of the antigen by axon-Schwann cell signals and cyclic AMP.

In the rat sciatic nerve, the relationship between Schwann cells, axons, the extracellular matrix and perineurial sheath cells undergoes extensive modification between embryo day 15 and the onset of myelination during the first postnatal day. Little is known about molecular changes in Schwann cells in this important prenatal period. In the present paper, we use immunofluorescence to study the prenatal development and postnatal regulation of the antigen(s) recognized by the 04 monoclonal antibody and a well-characterized rat monoclonal antibody to sulfatide, A007. We show that, in a series of immunochemical tests, the 04 antibody recognizes only sulfatide in neonatal and adult rat nerves. Both antibodies first bind to Schwann cells in the sciatic nerve at embryo day 16-17, and all Schwann cells bind both antibodies at birth. In the adult nerve, both nonmyelin-forming and myelin-forming cells are labelled with the antibodies. Schwann cells dissociated from embryo day 15 nerves and cultured in the absence of axons develop neither 04 nor A007 binding on schedule, and 04-positive and A007-positive Schwann cells from postnatal nerves lose the ability to bind these antibodies during the first few days in culture. Schwann cells in the distal stump of transected nerves also sharply down-regulate cell surface binding of 04. High numbers of 04-positive or A007-positive Schwann cells reappear in cultures treated with agents that mimic or elevate intracellular cAMP. We conclude that two anti-sulfatide antibodies 04 and A007, recognize an antigen, probably sulfatide, that appears very early in Schwann cell development (one to two days prior to galactocerebroside) but is nevertheless subject to upregulation by axonal contact or elevation of intracellular cAMP.

Animals↗
PubMed1990

Three markers of adult non-myelin-forming Schwann cells, 217c(Ran-1), A5E3 and GFAP: development and regulation by neuron-Schwann cell interactions.

Immunohistochemical methods are used to investigate in detail the development and regulation of three proteins (217c(Ran-1), A5E3 and GFAP) specifically associated with adult non-myelin-forming Schwann cells in the rat sciatic nerve, from embryo day 15 to maturity. 217c(Ran-1), which is probably the NGF-receptor, and A5E3 are expressed by the majority of cells in the nerve at embryo day 15 and by essentially all cells at embryo day 18. GFAP first appears at embryo day 18; this is an intrinsically programmed developmental event which occurs in cultured Schwann cells even in the absence of serum. Postnatally, the expression of 217c(Ran-1), A5E3 and GFAP is suppressed in cells that form myelin but retained in non-myelin-forming Schwann cells. Mature myelin-forming cells nevertheless maintain the potential to express all three proteins but will only do so if removed from contact with myelinated axons. In neuron-free cultures Schwann cells express all three proteins. This work, together with our previous observations on N-CAM, shows that removal of a diverse set of surface proteins and a change in intermediate filament expression is one of the major consequences of axon to Schwann cell signalling during myelination in the rat sciatic nerve. Unlike myelin-forming cells, adult non-myelin-forming Schwann cells remain very similar to embryonic and newborn cells with respect to expression of surface proteins, in contrast to the previously established developmental changes that occur in their surface lipids.

Animals↗
PubMed1990

Positive treatment.

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Acquired Immunodeficiency Syndrome↗
PubMed1988

Hyperfractionation of whole-abdomen radiation therapy: salvage treatment of persistent ovarian carcinoma following chemotherapy.

Whole-abdomen radiation therapy has been utilized as primary adjunctive therapy in the management of epithelial ovarian carcinomas with encouraging results. The results reported when using standard fractionation protocols in patients with recurrent or persistent ovarian carcinoma have been poor and treatment-related toxicities have been severe. There are reported theoretical and clinical advantages of hyperfractionation of ionizing radiation in treating malignancies. Fifteen patients have been treated with a twice-a-day whole-abdomen, open-field radiation technique delivering 80 cGy per fraction, to a total dose of 3040 cGy in 19 treatment days. All patients had Stage III epithelial ovarian carcinoma with persistent disease detected at pretreatment laparotomy after cis-platinum-based chemotherapy. All patients had moderately to poorly differentiated tumors with residual disease less than 1 cm. Acute side effects of treatment included mild to moderate nausea and diarrhea. Thrombocytopenia (less than 50,000) was noted in five patients. No bleeding or infectious complications were noted, and no patient required hospital admission for side effects. Disease recurred in nine patients with two still alive 13 and 52 months after starting irradiation. Six patients are currently alive without evidence of disease at follow-up, ranging from eight to 48 months. The mean survival to date is 20 months with four patients alive more than 2 years, and two patients alive for greater than 3 years from their radiation therapy. Patient tolerance has been acceptable, and both the short and long-term toxicities are minimal. Late side effects of treatment have not been noted. This technique offers a chance for a long, disease-free interval and possible cure in well-defined cases of chemotherapy-treated patients with persistent ovarian carcinoma.

Abdomen↗