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Biomedical subjects

L Morgan

Publications and source records attributed to L Morgan.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1988

Unrecognized invasive carcinoma in vulvar intraepithelial neoplasia (VIN).

Sixty-nine patients having had pretreatment biopsy diagnosis of vulvar intraepithelial neoplasia were treated with surgical excision of all visible lesions. Complete surgical specimens were submitted for pathological study in an attempt to identify occult invasive vulvar carcinoma. Unsuspected invasion was noted in 13 patients (18.8%). Superficial invasion (less than 1 mm) was seen in 8 patients, 4 had greater than 1 mm of invasion, and one verrucous carcinoma was identified. Patients of advancing age with disease that had a raised and irregular surface pattern were more likely to have lesions with occult invasion. Treatment that utilizes ablative techniques cannot be recommended based on the use of preoperative representative biopsies.

Adult↗
PubMed1988

The purification of four respiratory syncytial virus proteins and their evaluation as protective agents against experimental infection in BALB/c mice.

The fusion (F) glycoprotein, large glyco- (G) protein, phospho- (P) protein and 22K protein of respiratory syncytial (RS) virus A2 strain were purified by a combination of immunoaffinity adsorption and preparative SDS-PAGE. All four proteins elicited serum antibody in mice after repeated inoculation in adjuvant, although the magnitude of the response as measured by ELISA varied from mouse to mouse. The F protein generated neutralizing antibodies in only 50% of the mice determined to be seropositive by ELISA. The G protein also induced neutralizing antibodies but in this instance neutralization tests and ELISA titres were more closely correlated. No neutralizing activity was detected in mice immunized with the P or 22K proteins although all produced antibody detectable by ELISA. Mice immunized with either the F or the G protein were found to be protected against subsequent RS virus challenge, whether they had developed neutralizing antibody or not. Mice inoculated with the P or 22K proteins were not protected.

Animals↗
PubMed1987

Gardnerella vaginalis in prepubertal girls.

A prospective study was established to determine the significance of the isolation of Gardnerella vaginalis from the vagina in prepubertal children. Two hundred fifty-six children were enrolled. Group 1 consisted of 137 children who had been victims of sexual abuse; group 2, forty-eight children with genitourinary complaints and no history of sexual abuse; and group 3, seventy-one children with no genitourinary complaints and no history of sexual abuse. Gardnerella vaginalis was isolated from 20 patients (14.6%) in group 1 and five (4.2%) of 119 control patients from groups 2 and 3. Within group 1, G vaginalis was more likely to be isolated from children with a history of multiple episodes of sexual abuse than those with a single episode. Gardnerella vaginalis was not associated with any other historical, physical, or laboratory findings, including vaginal erythema or vaginal discharge.

Child↗
PubMed1987

Myelinated, but not unmyelinated axons, reversibly down-regulate N-CAM in Schwann cells.

There is evidence from chicks and mice that N-CAM expression in Schwann cells is subject to significant regulation during development and following injury. In the present work, rat sciatic nerve and immunohistochemical methods have been used to study developmental and injury-related modulation of N-CAM in Schwann cells, using cell type specific markers to identify different Schwann cell populations, and cell counting to quantify their size. The study has sought to determine unambiguously whether immature Schwann cells in developing nerves and denervated Schwann cells in injured adult nerves express surface N-CAM, and has investigated the temporal relationship between the gradual loss of surface N-CAM and the differentiation of myelin-forming Schwann cells, monitored by the sequential appearance of the glycolipid galactocerebroside and the myelin-specific protein P0. Further points examined are whether this down-regulation of N-CAM is rapidly reversible following loss of axonal contact, and whether N-CAM reappearance in Schwann cells depends on protein synthesis. In nerves from 17- to 18-day embryos, 90% of the Schwann cells, identified with Ran-1 antibodies, expressed surface N-CAM. In nerves from newborn rats many cells are in the early stage of myelin synthesis and therefore express galactocerebroside, although they have not yet acquired P0. Suspension staining of dissociated cells from this nerve showed that 92% of the galactocerebroside-positive cells were also N-CAM positive. In suspension staining of nerves from 5-day, 10-day and adult rats, P0-positive cells were essentially N-CAM negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Heterogeneity of the respiratory syncytial virus 22K protein revealed by Western blotting with monoclonal antibodies.

Respiratory syncytial (RS) virus-infected HeLa, HEp-2, Vero and BS-C-1 cell lysates were electrophoresed on SDS-polyacrylamide gels under reducing conditions and analysed by Western blotting and immunoperoxidase using monoclonal antibodies specific for the 22K protein (relative mol. wt. of 23,000 in our gel system). Three novel polypeptides with mol. wt. of 24,000, 21,000 and 17,000 were stained in addition to the 23,000 polypeptide which was present in the greatest amount in all three virus strains tested regardless of host cell line. When samples were electrophoresed under non-reducing conditions each of the three higher mol. wt. polypeptides seen in reducing gels migrated as two bands (total of six bands) with altered electrophoretic mobilities. In experiments using the alkylating agent iodoacetamide under conditions where the novel 24,000, 21,000 and 17,000 polypeptides were not visible, the number of mobility variants of the 23,000 polypeptide which could be detected in non-reducing conditions was increased from two to four. At least one, and possibly three, of these variants was the result of conformational variation in the 23,000 polypeptide caused by the generation or rearrangement of intrachain disulphide bonds after the infected cells were lysed in SDS-PAGE sample buffer. Post-lysis conformational changes were minimized by treatment of the infected cells with iodoacetamide before solubilization or by decreasing the SDS concentration or using milder detergents in the lysis buffer.

Antibodies, Monoclonal↗
PubMed1987

Expression of the respiratory syncytial virus 22K protein on the surface of infected HeLa cells.

Immunofluorescent staining of unfixed respiratory syncytial virus-infected HeLa cells with monoclonal antibodies (MAbs) demonstrated that the 22K protein is expressed on the cell membrane along with the fusion (F) protein and large glycoprotein (G). All three proteins were detected in the cytoplasm at 17 h post-infection and in the case of the F and G proteins this coincided with their appearance on the cell surface. However, the 22K protein could not be detected on the surface until approximately 16 h after its detection in the cytoplasm, when cytopathic effect was extensive. No evidence for the surface expression of the phosphoprotein (P), matrix (M) or nucleocapsid (N) proteins was found. Trypsin treatment of infected cells prior to unfixed immunofluorescent staining and Western blot analysis indicated that, unlike the G protein, the quantity of 22K protein detected on the cell surface constituted only a small proportion of the total present in the cell. A comparison of the patterns of immunofluorescent staining produced by MAbs on acetone-fixed infected cells suggested that the N, P and 22K proteins, but not the M protein, may be associated with the same intracellular structures.

Capsid↗