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Biomedical subjects

L Marks

Publications and source records attributed to L Marks.

At least 19 recordsLinked to original sources
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↗
PubMed1988

Infused and ingested labeled lysines: appearance in human-milk proteins.

Incorporation of two labeled forms of lysine into human-milk proteins was studied in fasted lactating subjects to determine whether highly labeled proteins could be produced for subsequent nutritional studies and whether the kinetics of milk synthesis could be studied in humans with stable isotope techniques. Five subjects, maintained on formula diets, received L-[13C1]lysine (27 mumol/kg) as an IV bolus and L-[15N2]lysine (27 mumol/kg) as an oral bolus 4 h postprandially. Milk samples were collected at 30, 45, 90, 150, 240, and 360 min. Tracer lysine levels in the hydrolysate of unfractionated milk protein were determined by gas chromatography-mass spectrometry isotope ratiometry. After a delay of at least 45 min, significant labeling of milk protein was detected and reached a maximum at 150 min with cumulative percent does recovery over 6 h of 0.5%. Human-milk proteins can be labeled for nutritional investigations and in vivo kinetics of milk protein synthesis can be studied with stable isotope techniques.

Administration, Oral↗
PubMed1988

Mobility after amputation for failed knee replacement.

Management of the failed total knee replacement is a formidable problem. In a 13-year period, 24 patients with above knee amputation following unsuccessful knee replacement were referred for prosthetic limb fitting. Adequate data was available for 23 patients. At review (or at the time of death), an average of 48.6 months after amputation, only seven of the 23 patients were regular daily walkers, although 10 patients had managed to walk for more than two years; 20 of the 23 used a wheelchair for some part of the day and 12 were confined to a wheelchair.

Activities of Daily Living↗
PubMed1986

New evidence for taurine biosynthesis in man obtained from 18O2 inhalation studies.

The ability of adult humans to synthesize taurine was assessed by measurement of the 18O content of urinary taurine in eight subjects following 60 minutes inhalation of 18O2 (97% 18O). All subjects had at least one 3-hour urine collection in which the mole ratio of 18O-taurine to taurine was at least three times greater than the standard deviation of the stable isotope measurement. The peak mole ratios of 18O-taurine/16O-taurine ranged from 0.0075 to 0.015. These data indicated that adult human subjects have a significant ability to synthesize taurine.

Adult↗
PubMed1986

Lysine and protein metabolism in young women. Subdivision based on the novel use of multiple stable isotopic labels.

A multitracer stable isotope study of lysine kinetics was carried out in fasted adult female volunteers to determine whether a multicompartmental model that partitions protein synthesis and breakdown into at least two types of tissue components can be constructed from plasma and breath data. Five female subjects, maintained on formula diets, received L-[13C1]lysine (27 mumol/kg) as an i.v. bolus and L-[15N2]lysine (27 mumol/kg) as an oral bolus 4 h postprandially. Plasma and breath samples were collected for 6 h. On an alternate day, subjects received NaH13CO3 (10 mumol/kg) as an i.v. bolus and breath samples were collected for 6 h. Plasma tracer lysine levels were determined by gas chromatography-mass spectrometry isotope ratiometry, and breath 13CO2 levels were measured by mass spectrometric gas isotope ratiometry. The tracer data could be fitted to a mammillary multicompartmental model that consisted of a lysine central compartment and slow- and fast-exchanging peripheral compartments containing 37, 38, and 324 mumol/kg, respectively. The rates of lysine oxidation, incorporation into protein, and release by protein breakdown were 21, 35, and 56 mmol/kg/h, respectively, in the fast-exchanging compartment, whereas the rates of protein synthesis and breakdown in the slow compartment were both 53 mmol/kg/min. These values corresponded to a whole-body lysine flux of 106 mmol/kg/h. The kinetic parameters were in excellent agreement with reported values obtained by constant-infusion methods. The measurements indicated that it will be possible to detect changes in amino acid pool sizes and protein synthesis and breakdown associated with the mobilization of protein stores from plasma and breath measurements in multitracer stable isotope experiments.

Administration, Oral↗
PubMed1978

Pressor response to saralasin (1-sar-8-ala-angiotensin II) bolus injection in hypertensive patients.

A 10 mg bolus of the angiotensin blocker saralasin was injected 113 times in 68 subjects with essential or renovascular hypertension. Ninety percent of injections caused a transient increase in blood pressure, which correlated with plasma renin activity (PRA) (r = -0.54); Mean increase at 2 minutes was 21/13.4 mm Hg (P less than 0.001) and was independent of pre-injection control blood pressure, with a rapid decrease to or below control values thereafter. Thirty-seven subjects were studied on successive days before and after furosemide-induced sodium depletion (152 +/- 26 mEq [SE] sodium loss). In the low renin group, sodium depletion did not change PRA or the magnitude of the pressor response to saralasin, but significantly decreased control MAP by 13 mm Hg (P less than 0.01). In normal and high renin patients, MAP was unchanged after diuresis, but PRA increased significantly and the pressor response was attenuated. The net effect of sodium depletion was to reduce the pressor response to saralasin in all renin subgroups by 9 to 12 mm Hg. Saralasin bolus injection, unlike infusion, saturates available vascular receptors only briefly, eliminating prolonged pressor responses.

Adolescent↗