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Biomedical subjects

L Morgan

Publications and source records attributed to L Morgan.

At least 109 records · Page 6Linked to original sources
PubMed1994

Negative regulation of the P0 gene in Schwann cells: suppression of P0 mRNA and protein induction in cultured Schwann cells by FGF2 and TGF beta 1, TGF beta 2 and TGF beta 3.

During the development of peripheral nerves, Schwann cells are induced to form myelin sheaths round the larger axons. This process involves a complex series of events and the nature of the molecular signals that regulate and control myelin formation in Schwann cells is not well understood. Our previous experiments on rat Schwann cells in vitro, using serum-free defined medium, showed that a myelin-related protein phenotype could be induced in early postnatal Schwann cells in culture by elevation of intracellular cyclic AMP levels in the absence of growth factors, conditions under which the cells are not dividing. Cells with this phenotype expressed the major myelin glycoprotein P0 and expression of p75 NGF receptor, N-CAM, GFAP and A5E3 proteins was down-regulated. These changes are all characteristics associated with myelination in vivo. In contrast, when cyclic AMP levels were elevated in the presence of serum, suppression of cyclic AMP-induced differentiation resulted and DNA synthesis was induced. In this paper, we have used this model system and extended our analysis to explore the relationship between defined growth factors and suppression of myelination. We have used pure recombinant growth factors normally present in peripheral nerves, i.e. FGF1 and FGF2 and TGF beta 1, TGF beta 2, and TGF beta 3 and shown that, like serum, they can strongly suppress the forskolin-mediated induction of the P0 gene, both at the level of mRNA and protein synthesis. For both growth factor families, the suppression of P0 gene expression is dose-dependent and takes place in serum-starved cells that are mitotically quiescent. In the case of FGF2, however, even more complete suppression is obtained when the cells are simultaneously allowed to enter the cell cycle by inclusion of high concentrations of insulin in the culture medium. The present results raise the possibility that, in addition to the positive axonal signals that are usually envisaged to control the onset of myelination, growth factors present in the nerve may exert negative regulatory signals during development and thus help control the time of onset and the rate of myelination in peripheral nerves.

Animals↗
PubMed1994

Thyroid disease in the elderly. Part 1. Prevalence of undiagnosed hypothyroidism.

BACKGROUND: The purpose of this study was to examine the prevalence of previously unrecognized hypothyroidism in elderly patients. METHODS: The study was conducted in a primary care geriatrics clinic. Three hundred seventy elderly patients (287 women, 83 men) between 60 and 97 years of age were included in the study. Medical records of patients were reviewed retrospectively. Serum thyroid-stimulating hormone (TSH), free thyroxine (T4), height, weight, demographic variables, clinical signs and symptoms of hypothyroidism, history of thyroid diseases and treatment with thyroid medications, comorbidities, and current medications were obtained from the medical records. Patients who had both elevated TSH levels (5.0 to 14.9 microU/mL) and normal free T4 levels (0.7 to 2.0 ng/dL) met the criteria for "subclinical hypothyroidism." The criteria for "overt hypothyroidism" were TSH levels > or = 15 microU/mL and low free T4 levels (< 0.7 ng/dL). RESULTS: At the initial visit to the clinic, 18.1% of the patients (62 female and 5 male) had an established history of past or current thyroid disease. Another 20 women (5.4%) had a history of thyroid surgery. Of the remaining 283 patients with no history of thyroid disease, 14.6% of the women and 15.4% of the men had subclinical hypothyroidism. Overt hypothyroidism was discovered and subsequently treated in two female patients and one male patient (1.0% and 1.3%, respectively). Thyroid status was not significantly related to age group (60 to 64 years; 65 to 74; 75 to 84; 85 and older). Comorbidities typically associated with hypothyroidism were no more prevalent in hypothyroid patients than in euthyroid patients. CONCLUSIONS: We found a high prevalence of newly diagnosed subclinical hypothyroidism in both elderly male and female patients. Thyroid status was not related to age or to coexisting diseases. The clinical significance of treating subclinical hypothyroidism merits investigation.

Aged↗
PubMed1994

Thyroid disease in the elderly. Part 2. Predictability of subclinical hypothyroidism.

BACKGROUND: The purpose of this study was to determine how well hypothyroidism could be predicted from clinical signs and symptoms in elderly patients with no known history of thyroid disease. METHODS: This retrospective study was conducted in a primary care geriatrics clinic. Two hundred eighty-three patients (205 women, 78 men), who were between the ages of 60 and 97 years of age and had no history of thyroid disease, were included in the study. Medical records of patients were reviewed for data obtained at their first visit to the clinic: serum thyroid-stimulating hormone (TSH), free thyroxine (T4), height, weight, demographic variables, clinical signs and symptoms of hypothyroidism, previous history of thyroid disease and treatment with thyroid medications, and current medications. RESULTS: Of the 283 patients with no previous history of thyroid disease, 15.4% of men and 14.6% of women had subclinical hypothyroidism (TSH levels of 5.0 to 14.9 microU/mL, and normal free T4 levels [0.7 to 2.0 ng/dL]). Overt hypothyroidism (TSH > or = 15.0 microU/mL, low free T4 < 0.7 ng/dL) was discovered and subsequently treated in one male and two female patients. There were no significant differences (P > .05) in the frequencies of any of the clinical signs and symptoms of hypothyroidism between euthyroid and hypothyroid patients. There was no significant relationship between TSH levels and the total number of hypothyroid symptoms experienced by all patients (r = -.004, P = .99). Logistic regression analyses determined that clinical signs and symptoms were poor predictors of subclinical hypothyroidism in these elderly patients. CONCLUSIONS: Thyroid status could not be predicted from clinical signs and symptoms in this sample of elderly community-dwelling patients. This finding substantiates the difficulty of diagnosing subclinical hypothyroidism in the elderly based solely on clinical features.

Aged↗
PubMed1993

Kinetics of interaction between normal and proline 12 Ras and the GTPase-activating proteins, p120-GAP and neurofibromin. The significance of the intrinsic GTPase rate in determining the transforming ability of ras.

Single turnover and equilibrium binding measurements on the interaction of Gly-12 and Pro-12 Ras.GTP with the catalytic domains of the GTPase-activating proteins, p120-GAP and neurofibromin, have been made utilizing fluorescent 2'(3')O-(N-methylanthraniloyl)-nucleotides. These have enabled the equilibrium dissociation constants (Kd) for their initial binding and the rate constants of the hydrolysis step to be measured. p120-GAP binds to both Ras proteins with a Kd of 17 microM, whereas neurofibromin binds to both Ras proteins with a Kd of 1 microM. Both p120-GAP and neurofibromin increased the rate constant of the GTP hydrolysis step of Pro-12 Ras, but the maximal activation at 30 degrees C was 120-fold and 560-fold, as compared with 70,000- and 52,000-fold, with Gly-12 Ras. The affinity with which p120-GAP and neurofibromin binds to either Gly-12 or Pro-12 Ras protein was decreased dramatically by increasing ionic strength caused by addition of NaCl. The rate constant of the cleavage step of hydrolysis catalyzed by neurofibromin increases with increasing ionic strength, whereas that catalyzed by p120-GAP appears to be unaffected. The high ionic strength within the cell might result in a much lower overall GTPase-activating protein activity than is measured under conditions of low ionic strength in vitro, with p120-GAP being more severely inhibited. The GTP hydrolysis rate of Pro-12 Ras is 2-fold faster than that of normal Ras. The low oncogenicity of Pro-12 ras is explained by a model in which the intrinsic rates of hydrolysis and exchange, as well as GTPase-activating protein- and exchange factor-stimulated rates, are determinants of the biological activity of Ras proteins in fibroblasts.

Cell Transformation, Neoplastic↗
PubMed1993

Changes in DNA synthesis rate in the Schwann cell lineage in vivo are correlated with the precursor--Schwann cell transition and myelination.

During the development of the rat sciatic nerve extensive proliferation of glial cells occurs, and there is a very substantial rearrangement of the cytoarchitecture as axons and Schwann cells assume relationships which lead to the formation of the myelinated and unmyelinated axons characteristic of adult nerve. The maturation of Schwann cells from Schwann cell precursors and the matching of Schwann cell numbers to axons is an important part of this process. We have therefore studied the proliferation of Schwann cell precursors and Schwann cells during the development of the rat sciatic nerve from embryonic day 14 to postnatal day 28 by combining bromodeoxyuridine injections of rats with double-label immunohistochemical techniques. The results reveal that DNA synthesis occurs in both Schwann cell precursors and Schwann cells throughout early nerve development. The labelling index is already substantial at embryonic day 14, but from embryonic day 17, when essentially all the glial cells have converted from precursor to Schwann cell phenotype, it rises sharply, peaking between embryonic day 19 and 20 before declining precipitously in the early postnatal period. This rapid decline in DNA synthesis coincides with the appearance of the myelin protein P0, and in individual cells DNA synthesis is incompatible with the expression of P0 protein. Nonmyelin-forming Schwann cells, which mature later in development, continue to synthesize DNA until at least postnatal day 15, but by day 28 essentially all Schwann cells in the nerve are quiescent.

Animals↗
PubMed1993

Local anaesthesia for eye surgery without a facial nerve block.

Traditionally, local anaesthesia for cataract surgery requires retrobulbar blockade to be supplemented with a facial nerve block in order to prevent blepharospasm. In this study retrobulbar block using a larger volume of local anaesthetic without facial nerve block is compared with the combined technique in 50 patients. The adequacy of the two techniques was assessed by the surgeon according to eye motility (in four different planes), lid motility and eye softness and an overall surgical assessment was made at the end of the procedure. Blepharospasm did not occur. The operating conditions were equally good in both groups (p > 0.05). These results suggest that good operating conditions for cataract operations can be provided by retrobulbar block alone without supplementary facial nerve block.

Aged↗
PubMed1993

Decisions regarding services for the frail elderly.

The care of the frail elderly will become a progressive challenge in the decades to come. There are presently validated and standardized measures for assessing the frail elderly, as well as a number of options for their care. The challenge for the physician will be the proper selection of assessment instruments and care options.

Activities of Daily Living↗
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↗