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Biomedical subjects

L C Allen

Publications and source records attributed to L C Allen.

At least 37 records · Page 2Linked to original sources
PubMed1984

An automated "high-pressure" liquid-chromatographic assay for hemoglobin A1c.

An automated "high-pressure" liquid-chromatographic assay for hemoglobin A1c is described. We use a 45-min incubation in acetate buffer (pH 5.5) to eliminate labile glycated hemoglobins. In this automated system conventional modules are used but it incorporates a solvent-switching valve to select either of two buffers, which differ in pH and NaCl concentration. The chromatographic column contains "polyCAT" (a weak cation-exchanger, polyaspartic acid linked to silica). Run time is 14 min per sample. The method is precise and results correlate well with those by other ion-exchange procedures.

Adolescent↗
PubMed1983

A clinical approach to the use of predictive values in the prenatal diagnosis of neural tube defects.

The rationale of calculating predictive values to interpret the amniotic fluid alpha-fetoprotein (AFP) test has been examined and applied to amniotic fluid AFP testing from one Canadian center. Such predictive value ccalculations may be misleading if they fail to make use of the actual magnitude of the test result or the results of other investigations. The alculation of predictive values has thus been extended to take into account magnitude of the test results, the clinical history, and the results of other investigations. The interpretation of an abnormal amniotic fluid AFP test that is followed by a normal result of a careful ultrasound scan of the fetal back is that there is a 54.5% chance that the fetus has spina bifida if there is a previous history of spina bifida. There is a 12.5% chance if there is a negative family history. These calculations lead to informed genetic counseling and rational decision making with regard to the continuation of the pregnancy.

Amniocentesis↗
PubMed1983

Alpha-fetoprotein and ultrasound scanning in the prenatal diagnosis of Turner's syndrome.

Based on data from 5 cases of fetal cystic hygroma (4 cases of Turner's Syndrome and one case of Trisomy 18) and one case of Down's Syndrome with severe subcutaneous oedema, it is concluded that amniotic fluid alpha-fetoprotein (AFP) is normal or only slightly elevated in such cases whereas AFP in fluid from the cystic structures is very high. Reported high values of 'amniotic fluid' AFP are therefore likely to have been obtained from fluids accidentally drawn from the cystic structures. Fluids from the two sources cannot be distinguished from each other visually. In support of this theory is that the maternal serum AFP was found to be normal in all cases where investigated. In the diagnosis of cystic hygromata detailed ultrasound scanning will reveal the correct diagnosis.

Adult↗
PubMed1982

Ultrasound and amniotic fluid alpha-fetoprotein in the prenatal diagnosis of spina bifida.

Amniotic fluid alpha-fetoprotein (AFP) assays and detailed ultrasound examinations were performed in 376 prenatal patients at risk for a neural tube defect (high-risk group). In addition, 2436 patients who underwent amniocentesis for other indications underwent preamniocentesis ultrasound screening and amniotic fluid AFP assays (low-risk group). There were 10 neural tube defects in the high-risk group (7 open and 3 closed) and 3 in the low-risk group (all open). Two of the 3 closed defects were detected prenatally. The predictive value of an elevated AFP level for an abnormal fetus was much higher in the high-risk (6 of 6, 100%) than in the low-risk group (1 of 6, 17%). When both ultrasound and AFP assay results were normal, the chance of a normal outcome was very high in both the high- and low-risk groups (99.7 and 100%, respectively). It was of particular interest that in the low-risk group, the likelihood of an abnormal outcome in women with elevated AFP and a normal ultrasonogram was low (0 of 5).

Amniocentesis↗
PubMed1981

The catalytic function of active site amino acid side chains in well-characterized enzymes.

Although the kinetics and types of reactions carried out by enzymes have been established for some time, the detailed chemistry performed by these catalysis is largely unknown. Their geometries and compositions are very different from those found in conventional chemistry and understanding their mechanisms will open new areas of chemistry and make important contributions to the rational design of pharmaceuticals. We have formulated a computational method for determining the electronic role of amino acid residues in the active sites of enzymes that have been well characterized by high resolution spectroscopy and other physical chemistry techniques. Ab initio electronic structure calculations with a good basis set were employed, and solvent and dielectric effects were taken into account. Applications were made to ribonuclease A, the serine proteases, the labile hydrogen bonds in acid proteases (pepsin), and carbonic anhydrase.

Binding Sites↗
PubMed1980

Amniotic fluid testosterone and follicle-stimulating hormone assay in the prenatal determination of fetal sex.

Amniotic fluid testosterone was assayed by radioimmunoassay in 812 samples taken at 16 weeks' gestation at the time of genetic amniocentesis. In each of 361 samples (45% of total), correct assignment of fetal sex was made where the testosterone level was above 33.8 ng/ml for male fetuses and below 16.2 ng/ml for female fetuses. In each of 159 of 353 (45%) samples assayed for follicle-stimulating hormone (FSH), levels were below 7.6 mlU/ml for male fetuses and above 10.9 mlU/ml for female fetuses. By combining the two assays in the testosterone/FSH ratio, correct assignment of sex was made in each of 282 samples (80%). The percentage of samples in which correct assignment was achieved was greater for female fetuses (ratio less than 2.2 in 161/187 [86%]) than for male fetuses (ratio greater than 3.4 in 121/166 [72%]). The testosterone/FSH ratio holds promise as a rapid biochemical screening tool in the prenatal diagnosis of fetal sex in X-linked disorders.

Amniocentesis↗
PubMed1980

Acetaldehyde hydrate and carbonic anhydrase: possible roles in the inhibition of brain aldehyde dehydrogenase.

One biochemical explanation for the chronic and addictive effects of ethanol involves a relationship between biogenic aldehydes, brain aldehyde dehydrogenase and acetaldehyde, the principal metabolic product of ethanol. We suggest here the possibility that acetaldehyde hydrate may act as an especially strong inhibitor of aldehyde dehydrogenase. Aldehyde hydrates are known to strongly inhibit aldehyde dehydrogenase as well as a number of other aldehyde oxidizing enzymes and it may be that acetaldehyde hydrate acts as a transition state or activated intermediate inhibitor. It is also suggested that carbonic anhydrase, which catalyzes the very rapid equilibrium between acetaldehyde and its hydrate, may play a role in this process.

Acetaldehyde↗
PubMed1980

The electrostatic potential of the alpha helix (electrostatic potential/alpha-helix/secondary structure/helix dipole).

The active sites of many enzymes are very close to the N-terminus of an alpha-helix. The helix dipole has been postulated to enhance the binding of anions and speed charge relays in catalysis. We present electrostatic potential maps of alpha-helices of various lengths using a point charge model. We show that the potential field of the helix can be mimicked by two equal and opposite charges, one at each terminus. The magnitude of these equivalent charges reaches its limiting value of +/- 0.2 to 0.3 electron at a helix length of approximately 7-10 residues. We also comment on the relative importance of the helix dipole to that of ionized residues in determining the electrostatics of a protein and discuss what consequences this has for enzymology.

Binding Sites↗
PubMed1980

High performance liquid chromatographic analysis of urinary catecholamines employing amperometric detection: references values and use in laboratory diagnosis of neural crest tumors.

We have developed an high performance liquid chromatographic procedure employing amperometric detection for the measurement of urinary free norepinephrine, epinephrine and dopamine. The between-day precision (C.V.) at various concentrations of the above analytes varied from 4.8-11.6%. There was negligible between-urine difference in the percent recovery of norepinephrine and epinephrine but considerable between-urine difference for dopamine. The procedure has been used to determine reference ranges in infants, children and adults. Its preliminary application to the laboratory detection of neural crest tumors is also described.

Adolescent↗
PubMed1979

Amniotic fluid lecithin/sphingomyelin ratio, palmitic acid, palmitic acid/stearic acid ratio, total cortisol, creatinine, and percentage of lipid-positive cells in assessment of fetal maturity and fetal pulmonary maturity: a comparison.

Lecithin/sphingomyelin (L/S) ratio, creatinine, percentage of lipid-positive cells, palmitic acid, palmitic acid/stearic acid (P/S) ratio, and total cortisol were analyzed as tests for fetal maturity and fetal pulmonary maturity in 164 samples of amniotic fluid from 121 patients. Fifty samples were taken within 72 hours of delivery. The best tests for fetal maturity (37 weeks) with differential percentages were L/S ratio, palmitic acid, and P/S ratio. In the assessment of fetal pulmonary maturity, we studied an additional 174 samples in which only L/S ratio, creatinine, and lipid-positive cells were analyzed. All tests showed a high predictive value of an immature (positive) result was much less for all six parameters; the three best tests were total cortisol (33%), lipid-positive cells (26%) and L/S ratio (14%).

Amniotic Fluid↗
PubMed1979

Assay of erythrocyte glucose-6-phosphate dehydrogenase on the GEMSAEC analyser.

A procedure for the assay of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) in erythrocytes on the GEMSAEC centrifugal analyzer using a modification of Beutler's procedure is described. Glucose-6-phosphate dehydrogenase activity is corrected for the contributing activity of 6-phosphogluconate dehydrogenase (EC 1.1.1.44) by using a two-cuvet system in which the activity of the sample incubated with 6-phosphogluconic acid is subtracted from the activity produced in the presence of the combined substrates, glucose-6-phosphate and 6-phosphogluconic acid. An overlay program on the GEMSAEC computer for calculation of results, and the use of a yeast glucose-6-phosphate dehydrogenase control which is stable frozen in dilute solution are discussed.

Centrifugation↗
PubMed1979

Coupling between oxidation state and hydrogen bond conformation in heme proteins.

In all heme proteins for which crystal structures are available, the N(epsilon) of a histidyl residue is bonded to the heme iron and N(delta) is hydrogen bonded to a carbonyl oxygen of the peptide backbone. We investigate here the possibility that a change in oxidation state of the iron or a change in the geometry of this hydrogen bond might change the hydrogen bond strength in a functionally significant way. Dimerization energies obtained from ab initio molecular orbital calculations on the hydrogen-bonded dimer of imidazole and planar formamide are used to represent the strength of this hydrogen bond in heme proteins. The effect of a change in iron oxidation state is modeled by varying the positive charge on imidazole. The effect of a change in hydrogen bond geometry is studied by employing x-ray coordinates for reduced and oxidized cytochrome c, deoxy- and metmyoglobin, and deoxy- and methemoglobin. Our conclusions are that the strength of this hydrogen bond in heme proteins is sensitive to both the oxidation state of the iron atom and to geometry changes on the order of those obtained from the x-ray coordinates. We speculate that the changes in oxidation state may be functionally coupled with changes in hydrogen bond geometry and that this hydrogen bond represents a feasible pathway to link protein conformation with redox potential or reactivity of the iron atom.

Animals↗