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Biomedical subjects

N Foster

Publications and source records attributed to N Foster.

52 records · Page 3Linked to original sources

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↗

GABA-agonist therapy for Alzheimer's disease.

Evidence suggesting a reduction of cerebral gamma-aminobutyric acid (GABA) neurons in Alzheimer's disease has been reported. To evaluate the possible contribution of GABA system dysfunction to the intellectual decline associated with this disorder, a controlled therapeutic trial of a potent and specific GABA agonist, THIP [4,5,6,7-tetrahydroisoxazolo(5,4,-c)pyridin-3-ol], was undertaken. Six Alzheimer patients with mild to moderately severe dementia and low spinal-fluid GABA levels received THIP at maximum individually tolerated dosage. No significant change in cognitive function could be discerned, despite attainment of dose levels that produced centrally mediated adverse effects similar to those of other GABA agonists. The results support the views that pharmacologic attempts to stimulate central GABA-mediated synaptic function may not confer therapeutic benefit to patients with Alzheimer's disease and that a GABA system deficit may not serve as a critical determinant of the dementia that characterizes this disorder.

Alzheimer Disease↗

The effects of exercise and weight loss on plasma lipids in young obese men.

We studied the independent and combined effects of exercise training and weight loss on blood lipids under fixed diet and exercise conditions. Twenty-one obese sedentary men were randomly allocated to one of four treatment groups: (1) inactive and constant weight (control), (2) exercise training and constant weight, (3) inactive and weight loss, and (4) exercise training and weight loss. There were three study periods: a 3 week baseline period inactive and on an isocaloric diet, a 12 week treatment period, and a 3 week weight stabilization period. Exercise consisted of treadmill walking at an energy cost of 3500 kcal/wk for groups 2 and 4 with replacement caloric intake only in group 2. Group 3 reduced caloric intake by 3500 kcal/wk during the treatment period. Weight loss for groups 3 and 4 were 13.4 pounds and 13.7 pounds, respectively. Maximal oxygen uptake (mL/min) increased 6% in both exercise groups (2 and 4), and percent body fat decreased only in these groups. Regression analysis by group assignment on HDL cholesterol (HDL-C) showed that the inactivity-weight loss modality (group 3) and the exercise-constant weight modality (group 2) each significantly increased HDL-C, with an additive effect of exercise and weight loss (group 4). The rate of HDL-C change differed significantly between groups (P = 0.01). HDL-C increased 0.63, 0.61, and 1.89 mg/dL per 3 weeks or 2%, 2.4%, and 5.5% above baseline levels in groups 2, 3, and 4, respectively, while the control group decreased 0.11 mg/dL. Plasma triglycerides and very low-density lipoprotein (VLDL) cholesterol increased with exercise at constant weight (group 2) and decreased with exercise associated with weight loss (group 4). In conclusion, exercise and weight loss separately and independently increase HDL-C, and their effects are additive.

Adult↗

Delineation of a transplanted malignant melanoma with indium-111-labeled porphyrin.

An indium complex of a cationic, water-soluble, synthetic porphyrin, tetra-4-N-methylpyridyl porphyrin tosylate, has been prepared and evaluated for its selective localization in tumors in Syrian Golden hamsters with flank transplanted malignant melanoma (Fortner MMI). Tumor-to-blood ratios of the compound increase from 42:1 at 6 hr postinjection, at which time activity levels in the tumor exceed those in all other tissues, to 162.1 at 72 hr. Images in one hamster at three time periods clearly delineated the tumor from nontarget background and also demarcated the viable and necrotic zones within the tumor itself.

Animals↗

The effect of alcohol on serum high density lipoprotein (HDL). A controlled experiment.

A cross-over study using 11 male subjects and a closely controlled diet, investigated the effect of alcohol on serum high density lipoprotein (HDL) components. Smoking status and body weight remained essentially constant and exercise changes were adjusted for in the analysis. As compared to sucrose, alcohol consumption was associated with a significant elevation in serum apolipoprotein A-I (0.37 mg/dl/g/day of alcohol) with similar effects for serum HDL cholesterol (0.14 mg/dl/g/day of alcohol) and serum apolipoprotein A-II (0.11 mg/dl/g/day of alcohol) achieving borderline levels of statistical significance.

Adult↗

Comparison of pergolide and bromocriptine therapy in parkinsonism.

Twenty-four parkinsonian patients compared pergolide and bromocriptine therapy in a randomized double-blind, two-period crossover study. Both drugs were adjusted to an optimal balance between benefits and side effects. The mean daily dose and dose range for pergolide and bromocriptine were 3.3 mg (0.7 to 7.2) and 42.7 mg (5.8 to 87.5), respectively. Adjunctive medications, which for most patients included levodopa (plus carbidopa), were not altered during the study. A similar spectrum of clinical effects was found with both drugs and with lisuride, which was used to treat 13 of the patients in a previous study. Despite neurochemical differences in the antiparkinsonian ergots, their clinical utility is quite similar. We draw attention to hepatotoxicity and pleural reactions that may occur rarely with these drugs.

Aged↗

Synthesis and evaluation of an 111In-labeled porphyrin for lymph node imaging.

111In-labeled tetra(4-N-methylpyridyl)porphyrin was investigated as a possible lymph node imaging agent. A clinically feasible method for the preparation of this radioactive pharmaceutical was developed from experiments with the synthesis and characterization of the unlabeled complex. The in vivo distribution of the compound in Wistar rats was determined as a function of time. Favorable lymph node-blood, lymph node-muscle, and specific lymph node-surrounding tissue ratios were obtained.

Animals↗

The effect of various vegetable supplements on serum cholesterol.

Several previous studies have indicated that vegetables may lower serum total cholesterol. This study, using a Latin square experimental design, investigates the effect of three vegetable supplements (vegetable roots, vegetable leaves and stalks, whole grains) on serum lipoprotein cholesterol. The results from each vegetable supplement are compared to the results from a sucrose supplement of equal caloric content. Dietary fat, alcohol consumption, cigarette smoking, body weight, and physical activity are all controlled in the experimental design or the analysis. The results show that the effect of vegetables on serum cholesterol is not confined to one vegetable grouping or one type of lipoprotein cholesterol. Vegetable leaves and stalks are associated with lower values of very low-density lipoprotein cholesterol (and possibly low-density lipoprotein cholesterol) and total cholesterol. Whole grains are associated with lower values of low density lipoprotein cholesterol and total cholesterol. In addition to the actual cholesterol lowering effect compared to sucrose, the lack of an increase, suggests some advantage in the use of these vegetable groupings (even roots) as a replacement for fat in the diet, and vegetable leaves and whole grains as a replacement for sucrose.

Adult↗

Epstein-Barr virus (EBV) antibody in patients treated by radical radiotherapy for head and neck cancer.

Antibody against Epstein Barr Viral capsid (EBV-VCA) was measured in 65 patients with primary head and neck cancer referred for radical radiotherapy. Sixty-three percent had locally advanced cancer and 37% had early disease. Forty-eight percent had detectable antibody in their sera. Thirty-three percent had elevated titers (above 1:20 dilution). Only 19% of cases with early cancer had increased titers. Almost 50% of those with locally advanced cancer or recurrence following treatment had titers above 1:20. A rise in titer within six months following radiotherapy was associated with a significant incidence of recurrence. There was no correlation between delayed hypersensitivity skin reaction to 2--4 dinitrochlorobenzene (DNCB) and titer values. EBV-VCA may be an additional parameter which can be used to determine host defenses in patients with malignancies.

Antibodies, Viral↗

The effect of diphenylhydantoin on the microbial assay of serum folate.

1. Two modifications fo the usual method of assay for folic acid in solutions are reported which appear to improve this procedure. These are a reduction of incubation time and dilution with 95% ethanol. 2. Experimental results are reported which indicate that Dilantin (5,5-diphenylhydantoin) does not interfere with the microbiological assay for folic acid.

Biological Assay↗

Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer's disease.

We hypothesized that 20 patients with isolated memory impairment (IMI) would demonstrate [18F]-2-fluoro-2-deoxy-D-glucose utilization and a progression of neuropsychological symptoms consistent with Alzheimer's disease (AD). IMI subjects performed similarly to AD in recall and verbal fluency, but comparable to normal subjects in other areas of cognitive functioning. A positron emission tomography (PET) diagnostic index based on parietal Z-scores categorized IMI patients into normal and abnormal metabolic patterns. Ten of the original 20 IMI patients (50%) reflected PET AD abnormalities. Clinical information was available for IMI patients at three-year follow-up. Ten (50%) had converted to AD, three were found to have pseudodementia and the seven remained IMI. Of the 10 IMI patients with an originally normal PET index, three (30%) were diagnosed with AD at three years. Of the 10 with an abnormal index originally, seven (70%) converted to AD. The finding that memory deficit in IMI was as pronounced as that in AD patients is consistent with the notion that memory is an initial symptom of AD. A substantial number of the IMI patients reflected regional hypometabolism similar to AD, suggesting that IMI is likely an early stage in progressive dementia. A large percentage of IMI patients converted clinically to AD within three years of initial study, though we observed impaired memory functioning well before a clinical diagnosis of AD could be made. In addition to potential clinical utility, IMI and PET represent an opportunity to study dementia in relation to brain chemistry at a time when brain pathology is in the process of development.

Aged↗

Carbon dioxide induced soybean protein precipitation: protein fractionation, particle aggregation, and continuous operation.

A novel protein fractionation technique using a volatile electrolyte has been developed. Carbon dioxide was used to isoelectrically precipitate 80% and 95% pure glycinin and beta-conglycinin fractions from soybean isolate. The protein fractions precipitated as primary particles 0.2-0.3 microm in diameter, which under optimum conditions may be recovered as aggregates up to 500 microm in diameter. The dependency of protein fractionation efficiency on aggregate settling rates has been demonstrated. The isoelectric points of the two main soybean fractions, glycinin and beta-conglycinin, were calculated to be pH 5.2 and 4.95, respectively. Solution pH was accurately controlled by pressure in the isoelectric pH range of the different soybean protein fractions, and a pH "overshoot" was eliminated. Volatile electrolyte technology was also applied to a continuous process in order to eliminate the particle recovery concerns associated with batch precipitation and to demonstrate the potential for scale-up. Glycinin was effectively recovered on-line (94% glycinin recovery) with a purity approaching that of the batch process (95%).

Biotechnology↗

Analysis of spectral changes in isotopically substituted porphyrins adsorbed on melanin surfaces by solid-state carbon-13 nuclear magnetic resonance spectroscopy.

Two synthetic, water-soluble porphyrins, tetra-4N-methyl-pyridyl porphyrin (T4NMPyP) and tetra-N,N,N-trimethylanilinium porphyrin (TMAnP), and their indium(III) complexes have been isotopically substituted for evaluation by solid-state NMR of their adsorption to melanin. Methyl carbons on the pyridyl and anilinium nitrogens on the periphery of the porphyrin are one site of substitution; the four equivalent meso carbons in the porphyrin ring are the second. Chemical shifts and line widths of the carbon resonances in the bulk porphyrins change after they are adsorbed on synthetic and natural melanins. These changes may be related to the predominant binding interactions involved in the adsorption process and suggest that chemisorption, involving strong interactions comparable to chemical bonds, occurs between charged groups in both ligand and substrate. Inhomogeneous line broadening of the resonances implies that variations in binding exist, which is in keeping with the known heterogeneous nature of the melanin polymer and the different steric demands of the porphyrin ligands. These solid-phase experiments illustrate the promise of NMR for elucidating information about the binding of soluble molecules to insoluble and structurally irregular biopolymers. Furthermore, they represent the first spectroscopic probe of the binding of cationic molecules to the biopolymer melanin in the solid state. Coupled with results from molecular modelling, they indicate that cationic porphyrins bind to melanin at similar sites.

Binding Sites↗