Search PubMed⌕ Search

Biomedical subjects

L Marks

Publications and source records attributed to L Marks.

At least 37 records · Page 2Linked to original sources
PubMed1996

Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system.

Ciliary neurotrophic factor receptor alpha (CNTFR alpha) is essential for normal embryonic development and may be involved in postnatal and adult neuronal maintenance. In addition, a rapidly growing body of evidence suggests that CNTFR alpha serves as a site of action for future growth factor therapeutics capable of treating a wide variety of disorders resulting from neuronal loss. We raised two polyclonal, anti-CNTFR alpha antisera against synthetic peptides corresponding to independent regions of rat CNTFR alpha. Western blot and immunohistochemical analyses indicated that affinity-purified preparations of both antisera specifically recognize CNTFR alpha. In the adult brain, the highest levels of CNTFR alpha immunoreactivity were found in the perikarya, dendrites and, occasionally, the axons of several distinct classes of neurons including hippocampal formation neurons, some sensory neurons, and many neurons involved in motor control. CNTFR alpha immunoreactivity also was concentrated in the following: perikarya, dendrites, and axons of ventral horn motor neurons in adult spinal cord; perikarya and axons of adult dorsal root ganglion neurons; and axons in adult peripheral nerve. In embryonic tissue, the highest levels of CNTFR alpha immunoreactivity were observed in differentiating neurons and their processes. Therefore, the present data suggest that CNTFR alpha serves several diverse functions in adulthood and during development.

Amino Acid Sequence↗
PubMed1995

Measurement of mevalonic acid in human urine by bench top gas chromatography-mass spectrometry.

Urinary excretion of mevalonate was reported to be correlated with endogenous cholesterol biosynthesis. A method is described whereby mevalonate (MVA) concentration in urine is determined by bench top gas chromatography-mass spectrometry after extraction as mevalonalactone (MVL) and conversion to mevalonolactone mono-TMS derivative. Within- and between-assay coefficients of variation were 4.02% and 8%, respectively. The mean concentration of MVA in 24-h urine collections from ten normolipidemic urinary subjects was 203 +/- 49.6 ng/ml (range: 44-576 ng/ml). Administration of 40 mg of Pravastatin (an HMG-CoA reductase inhibitor) significantly decreased (approximately 50%) the night concentration of MVA in five healthy volunteers. This assay could be useful for investigation of endogenous cholesterol synthesis rate in various dyslipidemias and in response to drug treatment.

Adult↗
PubMed1995

Effect of acetate and propionate on fasting hepatic glucose production in humans.

OBJECTIVE: Short chain fatty acids (SCFA, e.g. acetate and propionate) produced from bacterial colonic fermentation may be involved in the improvement of fasting glucose concentration observed with high dietary fibre diets. Because fasting blood glucose is related to hepatic glucose production, we have tested the effect of propionate and acetate on hepatic glucose production. SETTING: The study was carried out in the Clinical Research Center for Human Nutrition. SUBJECTS: Six healthy young volunteers. INTERVENTIONS: The subjects received, in a random order: acetate (12 mmol/h), or propionate (4 mmol/h), or acetate+propionate (12 mmol/h + 4 mmol/h), or an isotonic sodium salt solution (saline) in 3 h gastric infusions. Blood glucose and plasma insulin was monitored. Hepatic glucose production was measured with an isotopic method using [6,6-2H2] glucose. RESULTS: No changes were observed in blood glucose, plasma insulin concentrations or hepatic glucose production with any of the infused solutions. An increase in free fatty acid (FFA) plasma concentration related to the fasting state was observed with the saline solution, but not with the SCFA infusions (P < 0.05). There was also an increase in beta-hydroxybutyrate concentration with the saline and the acetate solutions, but not with the propionate or acetate+propionate solutions. CONCLUSIONS: SCFA, administered at a rate calculated on the basis of a continuous daily fermentation of 30 g dietary fibres, do not change hepatic glucose production or fasting blood glucose. Propionate and acetate decrease plasma FFA, and further studies are needed to explore this effect on glucose tolerance and insulin sensitivity.

Acetates↗
PubMed1995

[Oral hygiene of handicapped subjects in Flanders].

As part of an epidemiology survey within the population of handicapped 12-year old in Flanders this article describes several parameters related to oral health. On the average, it became obvious that oral hygiene had to be seriously increased. The presence of plaque and calculus is very typical for types 1, 2, 4 and 8. In addition, it is most striking to conclude that groups where a maximum of self-handiness is expected, do not score any better. The application of chemical controlling agents and the use of fluoride supplements is found extremely low. Finally, a lack was found, with respect to adequate oral hygiene instructions. There is a real need for in-service training programs for educators as well as for parents.

Belgium↗
PubMed1995

[Status of the teeth and degree of care in handicapped in Flanders].

In general, handicapped 12-year old do not show statistical relevant differences with non-handicapped age-matched children in Flanders regarding general caries prevalence, caries distribution and total caries experience. However, important differences were found for the restorative index showing a higher caries treatment need in handicapped children. When the results were analysed according to the type of handicapping condition, it was seen that children with borderline and mild mental handicap and children with speech-, language and/or learning difficulties show the most unfavorable picture. They have a high caries prevalence and caries experience and a low restorative index. Additional analysis of the results can throw some light on the presence of additional caries risk indicators and contributing caries risk factors.

Belgium↗
PubMed1994

Measurement of whole body acetate turnover in healthy subjects with stable isotopes.

Colonic fermentation of dietary fibres produces short-chain fatty acids (e.g. acetate, propionate). Measurements of whole body acetate turnover was used in order to estimate the production of colonic short-chain fatty acids in human subjects. However, higher flux rates for acetate have been reported in human studies with stable isotopes as compared to radioactive tracers. The reasons for this discrepancy are unclear. In this study, the stable isotope (1-13C)acetate was used and a method was developed to measure its enrichment in plasma. Variations between and within assays were less than 5%. The standard curve was linear from 0.5% to 10% enrichment. When this tracer was infused for 160 min in six healthy volunteers, acetate turnover was found to be 7.5 +/- 1 mumol kg-1 min-1, which is similar to data reported with radioactive tracers. We assumed that the higher flux rate previously observed with stable isotope tracers was related to differences in the physiological status of the subjects involved in these studies.

Acetates↗
PubMed1994

Rate of [15N]leucine incorporation and determination of nitrogenous fractions from gastro-jejunal secretion in fasting humans.

The aim of this study was to quantify the nitrogen fraction flow rates in gastro-jejunal secretions in fasting humans and to determine the [15N]leucine incorporation into the secreted proteins. A double lumen intestinal perfusion method was used in 5 healthy volunteers. Plasma and gastro-jejunal juices were collected during a 15-h intravenous [15N]leucine infusion. Total, soluble and insoluble nitrogen, amino acids and [15N]leucine enrichment were measured. The total nitrogen flow rate was 7.2 +/- 1.9 mmol.h-1 and 58% was ethanol soluble. The amino-acid composition remained constant and glycine was the most abundant. The plasma [15N]leucine enrichment at the isotopic plateau was 4.8 +/- 0.9 mol% excess. The [15N]leucine enrichment in the intestinal chyme increased asymptotically to reach a plateau after 5 h. The [15N]leucine enrichment at the plateau and the fractional synthesis rate of secreted proteins were 1.6 +/- 0.5 mol% excess and 21.5 +/- 3.3%.h-1, respectively. These results show that the composition of the basal gastro-jejunal secretion is very stable. A part of this secretion is composed of proteins with rapid synthesis rates.

Adult↗
PubMed1993

3-dimensional optimization of multiple arcs for stereotactic radiosurgery.

PURPOSE: During linear accelerator-based radiosurgery, the physicians and physicists need to determine which combination of treatment arcs are "best" with regard to target coverage and incidental dose to adjacent structures. This is a complex problem, especially when targets are geometrically close to critical structures. The purpose of this article is to present a method to mathematically determine a set of arcs to produce desired target and normal structure dose distributions in linear accelerator radiosurgery. METHODS AND MATERIALS: Nonlinear least squares regression was used to determine the table angles and gantry angle arc ranges and their associated beam weights appropriate to linear accelerator radiosurgery. RESULTS: Three cases are presented: (a) critical structure close to target volume; (b) target volume too large for the largest collimator to cover the volume with one isocenter and a standard plan; (c) target volume located within one critical structure and close to another critical structure. The optimized treatment plans are all shown to be superior to a defined standard plan. CONCLUSION: The method successfully enables one to determine nonstandard arcs which achieve the desired results. In particular, the method enables one to find clinical treatment solutions, even when the desired results cannot be a priori defined.

Humans↗
PubMed1991

Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia.

Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell pool in the majority of patients with ANLL. The agents were tested singly or sequentially, with a 1-hour incubation of the drugs preceding complement-mediated lysis using MY9. VP16 combined with Ara C killed up to 3.9 +/- 0.3 and 5.11 +/- 0.4 logs of the human ANLL cell lines HL60 and K562 at drug concentrations that killed only 1.2 +/- 0.1 logs of normal committed granulocyte/macrophage stem cells (CFU-GM). Adding a single exposure of the MY9 and complement (C') to the drug-treated cells, greater than 5.4 logs of HL60 were killed. Similar to other pharmacologic agents, no differential kill for clonagenic leukemic cells (colony-forming unit-leukemia; CFU-L) from patients with ANLL was seen for drug only treated blasts versus normal CFU-granulocyte-macrophage (CFU-GM), with less than 1 log CFU-L kill at drug concentrations that spared 1 log of CFU-GM. Similarly, only 1.1 +/- 0.3 logs of ANLL CFU-L were eliminated using MY9 and C'. However, with the sequential VP16/Ara C----MY9 + C' treatment, synergy was demonstrated and 2.6 +/- 0.3 logs of CFU-L were eliminated. Because CD33 is also found on the normal CFU-GM pool, two-stage long-term BM cultures were performed to determine pluripotent stem cell elimination by the drug/MoAb purging combination. No difference of CFU-GM or BFU-E production at 4 to 6 weeks of culture for VP16/Ara C, MY9 + C', or VP16/AraC----My9 + C' treated cells was seen compared with untreated controls indicating sparing of early progenitor cells. Sequential ex vivo treatment of human ANLL CFU-L with VP16/Ara C followed by complement-mediated lysis using MY9 synergistically kills CFU-L while sparing early normal hematopoietic progenitor cells, and thus may be a more effective way to purge BM than either alone.

Antibodies, Monoclonal↗
PubMed1991

Reversible neurotoxicity following hyperfractionated radiation therapy of brain stem glioma.

Two patients with brain stem gliomas were treated with hyperfractionated radiation therapy (HFR) (7,020 and 7,560 cGy, respectively). Despite initial clinical improvement during irradiation, both patients demonstrated clinical deterioration approximately 3 weeks after completion of radiotherapy. Cranial magnetic resonance imaging (MRI) revealed a progressive increase in distribution of abnormal brain stem signal consistent with either tumor or edema. 18FDG positron emission tomography (PET) was obtained in one patient and demonstrated a hypermetabolic lesion at diagnosis and a hypometabolic lesion at the time of clinical deterioration postirradiation. Management with a tapering dose of dexamethasone alone resulted in marked clinical (both patients) and radiographic (one patient) improvement, allowing reduction or discontinuation of this medication. These results suggest that patients with brain stem tumors demonstrating clinical and radiographic evidence of progressive tumor shortly after completion of HFR should be initially managed conservatively with dexamethasone, since these findings may be manifestations of reversible radiation-related neurotoxicity.

Adolescent↗
PubMed1991

Branched-chain amino acid interactions with reference to amino acid requirements in adult men: valine metabolism at different leucine intakes.

We explored whether the oxidation of valine and by implication the physiological requirement for this amino acid are affected by changes in leucine intake over a physiological range. Six young adult men received, in random order, four L-amino acid-based diets for 5 d supplying either 20 or 10 mg valine.kg body wt-1.d-1, each in combination with 80 or 40 mg leucine.kg-1.d-1. On day 6 subjects were studied with an 8-h continuous intravenous infusion of [1-13C]valine (and [2H3]leucine) to determine valine oxidation in the fasted state (first 3 h) and fed state (last 5 h). Valine oxidation in the fasted state was similar among all diets but was lower (P less than 0.05) in the fed state for the 10 vs 20 mg valine.kg-1.d-1 intake. Leucine intake did not affect valine oxidation. Mean daily valine balance approximated +1.3 mg.kg-1.d-1 for the 20-mg intake and -1.6 mg.kg-1.d-1 for the 10-mg intake. These findings support our previously suggested mean valine requirement estimate of approximately 20 mg.kg-1.d-1.

Adult↗
PubMed1991

Branched-chain amino acid interactions with reference to amino acid requirements in adult men: leucine metabolism at different valine and isoleucine intakes.

Recent estimates of the leucine requirement of adult men based on 13C-tracer studies are substantially higher than those proposed by FAO/WHO/UNU (1985). To explore whether leucine oxidation and requirements are affected by the dietary amount of valine. 11 healthy young adult men received, in random order, for 5 d, one of four L-amino acid diets providing 40 or 15 mg leucine.kg-1.d-1 together with variable amounts mg.kg-1.d-1 of valine and isoleucine in the following combinations (Val:Ile): 80:62 and 20:62 (six subjects; phase 1); 20:62 and 20:20 (five subjects, phase 2). On the morning of day 6, a continuous intravenous infusion of L-[1-13C]leucine was given for 7-8 h; the subject was in the fasting state for the initial 2.5 or 3 h and in the fed state for the remainder of the time. Also, [2H3]leucine was added to the diet. Leucine oxidation was similar for all diet groups in the fasted state. During the fed state, leucine oxidation was not affected by the Val:Ile pattern. Thus, changes in the pattern of branched-chain amino acid intake within a physiological range do not affect isotopically derived estimates of the leucine requirement.

Adult↗
PubMed1990

Effect of multiple firing on the bond strength of selected matched porcelain-fused-to-metal combinations.

In this study two different opaque porcelain-metal combinations were evaluated for planar shear bond strength. Samples were tested after one, three, five, seven, and nine different firing cycles to evaluate the effect of repeated firing on shear bond strength. For the combination of Will Ceram/W1 and Vita/Olympia materials, no statistical difference was observed either between materials or after repeated firing. For apparently well-matched porcelain-metal combinations, no significant reduction in bond strength occurs during normal firing of the opaque porcelain to the metal.

Analysis of Variance↗
PubMed1990

Phenylalanine flux in adult men: estimates with different tracers and route of administration.

The kinetics of three different tracers of phenylalanine were studied when continuously infused together either by an intravenous (IV) or intragastric (IG) route in six young healthy men during a fasting state. During IV infusion, mean flux values were 39.2 +/- 1.8, 40 +/- 3, 41.8 +/- 3.6 mumol.kg-1.h-1 for L-[ring-2H5], [15N], and L-[1-13C]phenylalanine, respectively (differences not significant). Fluxes were higher (P less than .001) during IG than IV infusion, indicating a disappearance of tracer during the first pass through the splanchnic area. Also, higher fluxes were found for [ring-2H5]phenylalanine (74 +/- 6.23 mumol.kg-1.h-1) compared with [15N] and L-[1-13C]phenylalanine (54.24 +/- 4.7 and 61.15 +/- 5.3 mumol.kg-1.h-1) during IG infusion. Proton exchange might explain this difference, possibly limiting in vivo use of this label when the tracer is to be administered by the IG route.

Adult↗