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Biomedical subjects

S Manuel

Publications and source records attributed to S Manuel.

15 recordsLinked to original sources
PubMed2003

Survival in patients under 45 years with squamous cell carcinoma of the oral tongue.

Squamous cell cancer among young adults is rare and thought to have aggressive biological behaviour and poor prognosis. Clinical case records of 76 patients under the age of 45 years treated for squamous cell carcinoma (SCC) of the oral tongue were retrospectively analysed to calculate the survival rates and the predictors of survival. The overall survival (OS) and disease free survival (DFS) at 5 year were 78.0% and 57.4% respectively. Tumour status, pathological node status, surgical clearance, the selection of appropriate treatment, type of primary and neck surgery, were found to significantly influence the survival rates. Young patients with SCC of the oral tongue were seen to have a comparable outcome and prognosis compared to that in older patients.

Adult↗
PubMed2002

Carcinosarcoma of the parotid gland with epithelial-myoepithelial carcinoma and pleomorphic sarcoma components.

We report a case of true malignant mixed tumour (carcinosarcoma) of the parotid gland with epithelial-myoepithelial carcinoma and pleomorphic sarcomatous components in a 68-year-old woman. The pleomorphic sarcomatous component behaved aggressively with lymph node and distant metastases. The biological behaviour of the individual components in a malignant mixed tumour makes it difficult to diagnose. We could find no previous report of epithelial-myoepithelial carcinoma as a component of a carcinosarcoma of the parotid.

Aged↗
PubMed1999

Implementing a latex safe environment in a hospital setting. Case study.

1. Change is a difficult process. Using a change model as a guide to implementing change can make the process easier. 2. Hospitals work well using the team approach to accomplishing change. Representation from all key areas of the hospital is essential. 3. It is important to educate resisters regarding the benefit and need for change. The strongest opponents can become the strongest leaders in the change process. 4. Education cannot be underestimated. It is essential to use formal and informal means to educate all personnel.

Hospitals, Community↗
PubMed1994

Evidence that modulation of glucose transporter intrinsic activity is the mechanism involved in the allose-mediated depression of hexose transport in mammalian cells.

In serum starved V79 Chinese hamster lung fibroblast cells, replacement of D-glucose with D-allose resulted in a significant 38 +/- 18% (P < 0.05) reduction of 2-deoxy-D-glucose (2-DG) transport. Similarly, in a respiration-deficient mutant cell line (V79-G14), which has elevated 2-DG transport activity, D-allose reduced 2-DG transport by 59 +/- 18% (P < 0.05). [3H]D-allose uptake by V79 cells occurred slowly and was not inhibited by cytochalasin B, suggesting diffusion as the mode of D-allose entry. Western blot analysis using a rabbit polyclonal antibody to the human erythrocyte glucose transporter (GT) demonstrated that, in both cell lines, GT content and GT subcellular distribution were not significantly different in D-glucose vs. D-allose-treated cells. delta-Antibody, which has been shown to bind to exofacial epitopes of the GT (Harrison et al., 1990, J. Biol. Chem., 265:5793-5801), did not demonstrate any differences in surface binding to D-glucose vs. D-allose-treated intact V79 cells. D-allose treatment of 3T3 fibroblasts resulted in a similar decrease (72%) of 2-DG transport, however D-allose had no apparent effect on basal sugar transport in 3T3 adipocytes. These results suggest that D-allose reduces sugar transport through a modulation of the intrinsic activity of the GT, and that D-allose may act in a tissue-specific manner.

3T3 Cells↗
PubMed1993

Coordinate regulation of triacylglycerol synthesis and glucose transport by acylation-stimulating protein.

Acylation-stimulating protein (ASP) is the most potent recognized stimulant of triacylglycerol synthesis in human adipocytes. However, its mechanism(s) of action have not yet been elucidated in detail. The present study examines the effects of ASP on membrane transport of glucose and fatty acids in cultured human skin fibroblasts. The data demonstrate that ASP stimulated carrier-mediated glucose transport in a time- and concentration-dependent manner, an effect that was greater than and independent of that observed with insulin. ASP increased the Vmax for glucose transport with no change in the transport Km, suggesting that ASP might result in increased sugar transporters in the plasma membrane. This finding was supported by quantitative Western blot analyses using a monoclonal antibody (G3) that demonstrated an increase in the plasma membrane content of the glucose transporter (Glut 1) with a concomitant decrease in the glucose transporter content of an intracellular membrane fraction. By contrast, ASP had no effect on specific membrane transport of fatty acids. Maximal effects of ASP on triacylglycerol synthesis were demonstrated at saturating levels of both glucose and oleate. Comparable stimulation by ASP in the absence of glucose (with or without pyruvate) was also demonstrated, although the absolute rates of triacylglycerol synthesis were substantially lower. Finally, it was shown that ASP increased the apparent Vmax for triglyceride synthesis without changing its Km. Since ASP will act in the absence of extracellular glucose, ASP must have additional actions, independent of its effect on specific membrane transport of glucose by which it accelerates intracellular triglyceride synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1992

Inhibitors of protein synthesis cause increased hexose transport in cultured human fibroblasts by a mechanism other than transporter translocation.

We have investigated the effect of various inhibitors of protein synthesis on hexose transport in human skin fibroblasts using 2-deoxy-D-glucose (2-DG) and 3-0-methyl-D-glucose (3-OMG) to measure hexose transport. Exposure of glucose-fed, serum-free cultures to cycloheximide (CHX) (50 micrograms/ml) for 6 h resulted in increased 2-DG transport (3.81 +/- .53 vs. 6.62 +/- .88 nmoles/mg protein/2 min; n = 9) and 3-OMG transport (1.36 +/- .66 vs. 3.18 +/- .83 nmoles/mg protein/30 sec; n = 4) in the CHX exposed group. Under these conditions inhibition of protein synthesis was greater than 90%. This CHX induced transport increase was time dependent (approaching maximum within 1 h of exposure to CHX) and related to an increase in the Vmax of hexose transport in the CHX exposed group (18.4 +/- 2.4 vs. 4.8 +/- 1.1 nmoles 2-DG/mg protein/min) with no difference in the transport Km (1.55 +/- .63 vs. 2.92 +/- .59 mM). Further, the CHX induced increase in hexose transport was reversible. Exposure of human fibroblasts to inhibitors of protein synthesis with different mechanisms of action (e.g., puromycin, pactamycin, or CHX) all generated hexose transport increases in a concentration-dependent fashion correlating with their increasing inhibitory effects on protein synthesis. Nucleotidase enriched (i.e., plasma membrane) fractions of control and CHX-exposed cells showed no differences in D-glucose inhibitable cytochalasin B binding activity. Further, quantitative Western analysis of nucleotidase enriched fractions indicated CHX exposure resulted in no significant increase in glucose transporter mass compared with control plasma membrane fractions. Glucose deprived cells, however, which exhibited increased sugar transport comparable to the CHX-exposed group, did show increased glucose transporter mass in the plasma membrane fraction. The data indicate that inhibitors of protein synthesis can cause a significant elevation in hexose transport and that the hexose transporter mass in the isolated plasma membrane fractions did not reflect the whole cell transport change. It is suggested that a mechanism other than glucose transporter translocation to the plasma membrane may be involved in causing this sugar transport increase.

3-O-Methylglucose↗
PubMed1990

Characterization of the D-allose-mediated regulation of sugar transport in Chinese hamster fibroblasts.

Exposure to D-allose has been demonstrated to lead to decreased 2-deoxy-D-glucose (2-DG) and 3-0-methyl-D-glucose transport in the V79 Chinese hamster lung fibroblast cell line. The effect of D-allose 1) was maximal after 4 hours exposure to the cells; 2) was optimal between 2.77 and 5.55 mM D-allose; and 3) led to a decreased Vmax for 2-DG transport with no change in the transport Km value. The decrease in 2-DG transport induced by D-allose was reversible and the reversal was differentially affected by cycloheximide, being blocked by a low concentration of cycloheximide (0.05 micrograms/ml) but not a high concentration of the inhibitor (5 micrograms/ml). D-allose did not competitively inhibit the transport of 2-DG while D-glucose under similar conditions yielded a Kl for 2-DG transport inhibition of 1.7 mM. Additionally, D-allose did not affect the phosphorylation of 2-DG by hexokinase in cell-free cytosol. The data indicate that D-allose has significant lowering effects on sugar transport activity. Additionally, while the sugar itself may be the active component in sugar transport regulation, the effect is not blocked by inhibition of protein synthesis but the synthesis of a regulatory protein(s) may be involved in the return of sugar transport following D-allose removal.

Animals↗
PubMed1989

Discovering phonetic coherence in acoustic patterns.

Despite spectral and temporal discontinuities in the speech signal, listeners normally report coherent phonetic patterns corresponding to the phonemes of a language that they know. What is the basis for the internal coherence of phonetic segments? According to one account, listeners achieve coherence by extracting and integrating discrete cues; according to another, coherence arises automatically from general principles of auditory form perception; according to a third, listeners perceive speech patterns as coherent because they are the acoustic consequences of coordinated articulatory gestures in a familiar language. We tested these accounts in three experiments by training listeners to hear a continuum of three-tone, modulated sine wave patterns, modeled after a minimal pair contrast between three-formant synthetic speech syllables, either as distorted speech signals carrying a phonetic contrast (speech listeners) or as distorted musical chords carrying a nonspeech auditory contrast (music listeners). The music listeners could neither integrate the sine wave patterns nor perceive their auditory coherence to arrive at consistent, categorical percepts, whereas the speech listeners judged the patterns as speech almost as reliably as the synthetic syllables on which they were modeled. The outcome is consistent with the hypothesis that listeners perceive the phonetic coherence of a speech signal by recognizing acoustic patterns that reflect the coordinated articulatory gestures from which they arose.

Adult↗
PubMed1987

Hexose transport regulation in cultured fibroblasts derived from normal and type II diabetic patients.

The kinetics of saturable and nonsaturable sugar transport were studied in normal and Type II diabetic cultured skin fibroblasts under fast or slowly growing conditions. The Km of hexose transport for fast and slow-growing normal fibroblasts was 1.38 +/- 0.3 and 0.88 +/- 0.12 mM, respectively, while those of the diabetic fibroblasts were 1.57 +/- 0.29 and 0.8 +/- 0.19 mM, respectively. The respective transport Vmax for normal and diabetic fast-growing cells was 13.9 +/- 0.8 and 12.95 +/- 2.4 nmoles 2-DG/mg protein/min. For slowly growing cells of both groups, a transport Vmax of 11.5 +/- 2.4 and 11.3 +/- 1.7 nmoles 2-DG/mg protein/min was obtained. No significant differences were observed in the Km or Vmax of hexose transport under these various growth conditions between normal and diabetic cell cultures. Nonsaturable sugar uptake as determined by L-glucose or cytochalasin B inhibited 2-DG uptake was variable, but no significant differences were observed between the normal and Type II diabetic cells. The activation energies for saturable and nonsaturable sugar uptake were not different among the two donor groups. Insulin stimulation of hexose transport was studied in the presence and absence of dexamethasone (5 X 10(-6) M) at varying insulin concentrations. No difference was observed in the amount of insulin necessary to obtain a maximum stimulatory response (approximately 33 nM insulin in both groups). Also, the insulin concentration required to achieve a one-half maximal response was not significantly different in the donor groups (i.e., 3.53 +/- 0.6 nM for normals and 3.98 +/- 1.1 nM for diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Characteristics of normal and maturity-onset diabetic (type II diabetes) cell cultures: life spans and DNA synthetic capabilities.

The replicative ability of fibroblasts derived from normal and type II diabetic (non-insulin-dependent) donors and their DNA synthetic capabilities in response to serum and insulin (+/- dexamethasone) have been studied. Comparative replicative life spans of the fibroblasts studied using several lots of serum showed no significant differences between the two donor groups with any lot of serum (p greater than 0.05). Insulin (i.e. 700 nM) and serum (10% v/v) stimulation of DNA synthesis in normal and type II diabetic cultures exhibited no differences in responses. The insulin:control ratios of the normal vs. type II diabetic were 1.61 +/- 0.08 vs. 1.81 +/- 0.11, respectively (p greater than 0.05) while the serum:control ratios were 3.55 +/- 0.58 vs. 4.02 +/- 0.54, respectively (p greater than 0.05). Dexamethasone amplification of the insulin-stimulated DNA synthetic response over a range of insulin concentrations (i.e. 1.6-66.6 nM) expressed no differences between the two donor groups. Additionally, calculation of the insulin concentration necessary for the half-maximal response showed no differences between the normal and diabetic groups (3.47 +/- 0.5 vs. 4.44 +/- 0.8 nM, respectively) (p greater than 0.05). The data suggest that there are no general age-related abnormalities inherent to the type II diabetic cultured cell.

Adult↗
PubMed1985

Control of sugar transport in human fibroblasts independent of glucose metabolism or carrier-substrate interaction.

Transport regulation by different metabolizable and nonmetabolizable sugars was studied in human fibroblasts. Sugars were classed as glucose-like (D-mannose, 3-0-methyl-D-glucose, thio-D-glucose, and D-allose) and starvation-like (D-galactose, D-fructose, L-glucose, D-xylose, 6-deoxy-D-glucose and 2-deoxy-D-glucose) based on their competence in curbing glucose starvation enhanced transport. No significant correlation existed between the ability of a sugar to curb hexose transport and the KI of that sugar in inhibiting hexose transport. Independence of the transport curb from glucose metabolism was observed since nonmetabolizable analogs of D-glucose when substituted for D-glucose in the culture medium effected glucose [i.e. 3-0-methyl-D-glucose (3-OMG)] and starvation-like (i.e. 6- and 2-deoxy-D-glucose) effects. The KI of inhibition pf 2-deoxy-D-glucose transport for 3-OMG was 8.5 mM, similar to those obtained for 6-deoxyglucose and 2-deoxyglucose on 2-deoxyglycose transport (7.5 and 3.5 mM, respectively) and on 3-0-methylglucose transport (3.5 and 2.5 mM, respectively). An equimolar mixture of D-glucose and 3-OMG (5.55 mM each) was more effective than 11.1 mM D-glucose or 3-OMG alone in curbing hexose transport or reversing hexose starvation induced increases in transport. The effect of 3-OMG may be independent of glucose metabolism but it is possible that 3-OMG structurally mimics a metabolite of glucose that may interact with intracellular regulators of carrier degradation and or expression.

3-O-Methylglucose↗
PubMed1983

Enhanced insulin stimulation of sugar transport and DNA synthesis by glucocorticoids in cultured human skin fibroblasts.

Glucocorticoids will enhance the growth of cultured human skin fibroblasts in serum-containing medium. In serum-free cultures hydrocortisone (5 X 10(-6) M) will enhance insulin stimulation of sugar transport and DNA synthesis (as measured by thymidine incorporation into trichloroacetic acid-precipitable material). The optimal concentration for the glucocorticoid effect on DNA synthesis was 5 X 10(-8) M for dexamethasone and 5 X 10(-7) M for hydrocortisone. In dexamethasone-treated cells, concentrations of insulin as low as 250 microU/ml (10 ng/ml) were effective in stimulating DNA synthesis. Further, hydrocortisone and dexamethasone (both at 5 X 10(-6) M) exhibited potentiating effects on insulin-stimulated sugar transport. These effects appeared to be mediated via inhibitory actions on the hexose transport system with the preservation of a functional insulin-receptor interaction resulting in insulin stimulation of deoxy-D-glucose transport at physiological insulin concentrations, 250 microU/ml (10 ng/ml). Hydrocortisone also enhanced specific [125I]insulin binding in these cells. The data indicate that the mechanism(s) of glucocorticoid enhancement of two actions of insulin may be different.

Biological Transport, Active↗
PubMed1982

Regulation of sugar transport in cultured diploid human skin fibroblasts.

The regulation of hexose transport under glucose-starvation conditions was studied in cultured human skin fibroblasts. Glucose starvation enhanced the transport of 2-DG and 3-0-methyl-D-glucose (3-OMG) but not of L-glucose. Glucose-starvation enhanced transport was inhibited by cytochalasin B (10 microM). The starvation-induced change in 2-DG transport was due to an increase in the Vmax of both the high and low affinity transport sites (2.8- and 2.4-fold, respectively) with no effect on their Kms. The presence of 5.55 mM glucose, fructose, or L-glucose in the medium resulted in transport increases similar to those seen in glucose-starved cells, while the presence of 5.55 mM glucose, mannose, or 3-OMG repressed 2-DG transport. Glucose-starvation enhancement of 2-DG transport was blocked by cycloheximide (20 micrograms/ml) but not by actinomycin D (0.03 microgram/ml) or alpha-amanitin (3.5 microM). Readdition of glucose (5.55 mM) for six hours to glucose-starved cells led to a rapid decrease in hexose transport that could be blocked by cycloheximide but not actinomycin D. Although readdition of 3-OMG to glucose-starved cells had little effect on reversing the transport increases, glucose plus 3-OMG were more effective than glucose alone. Serum containing cultures (10% v/v) of glucose-fed or glucose-starved cells exhibited rapid decreases in 2-DG transport when exposed to glucose-containing serum-free medium. These decreases were prevented by employing glucose-free, serum-free medium. The data indicate that hexose transport regulation in cultured human fibroblasts involves protein synthesis of hexose carriers balanced by interactions of glucose with a regulatory protein(s) and glucose metabolism as they affect the regulation and/or turnover of the carrier molecules.

3-O-Methylglucose↗
PubMedDate not supplied

Development of an exercise expert system for older adults.

The purpose of this study was to develop a computerized exercise expert system (CEES) that creates tailored exercise plans for older adults. A panel of experts was selected in the areas of medicine, exercise physiology, health promotion, exercise psychology, and gerontology. The experts communicated with the principal investigator and the project members by mail, email, telephone, and expert meetings. A two-day workshop was held during the second year for the project members as well as local and national experts to review the CEES. The CEES demonstrated adequate inter-rater reliability (0.80) and criterion validity (0.70). Content validity was achieved by literature review and expert opinion. The CEES gathers information on the elder's health status, clinical factors, and exercise determinants that characterize specific barriers or incentives to exercise. The software program then develops individualized exercise prescriptions that are customized to older adults.

Adult↗