bluuebunny/crossref_metadata_2025 huggingface dataset:
Observations Concerning Pentosuria and Labile Phosphate Excretion in Muscular Dystrophy
Authors: Abel Francis L , Routh J I , Shepherd James A , Utterback R A
Published: January 2020

Early attempts to confirm the presence of pentose in urine from dystrophic patients by paper chromatography were unsuccessful. We were unable to confirm these observations, employing the same methods used in the original publication. An attempt to isolate pentosazone from the urine of dystrophic patients yielded 1-phenylsemicarbazide. No significant excretion of labile organic phosphate was found in urine from either vitamin E-deficient rabbits or cholinedeficient rabbits.

Column chromatographic methods were developed for the separation of pentosazones from hexosazones, and for the purification of osazones in lieu of recrystallization. Two solvent systems are described that will separate osazones from 1-phenylsemicarbazide, using ascending paper chromatography, but that do not separate osazone mixtures.

Using these latter methods, it was found that pentoses were excreted in both muscular dystrophy and normal urines. Evidence is presented that explains the widely divergent results obtained by others in attempting to confirm Minot's work using the osazone test.
Improved Method for the Determination of Hemoglobin A2 by Starch-Gel Electrophoresis
Authors: J. Goldberg C A , Ross A C
Published: January 2020

It has been shown that variations in the preparation of the starch gel and in photographic interpretation can significantly affect the accuracy of the measurement of hemoglobin A2.

An improved method for the determination of hemoglobin A2 by starch-gel electrophoresis has been presented which affords greater accuracy than was previously achieved.

Hemoglobin A2 concentrations for healthy persons and patients with sickle cell trait, various nonthalassemic anemias, and thalassemia trait have been presented.
Direct Ultramicro Glucose Oxidase Method for Determination of Glucose in Biologic Fluids
Authors: Kingsley George R , Getchell Gloria
Published: January 2020

A simple, direct, ultramicro, specific-enzyme method for determination of plasma and urine glucose is described in detail and compared with other methods.
Use of a New Assay in a Study of Serum Alkaline Phosphatase Levels in 2000 Hospital Patients
Authors: Babson Arthur L , Read Prunella A , Phillips George E , Luddecke Hugh F
Published: January 2020

Serum alkaline phosphatase determinations performed with a commercially available tablet procedure for rapid semiquantitative assay gave results that were found to be reliable and in agreement with quantitative assays performed by the Bodansky procedure.

In a study of the sera of 2000 hospital patients, more than 70 per cent of all the assays requested yielded normal values. Since precise determinations in the normal range are generally not required for clinical interpretation, routine use of the semiquantitative test for preliminary screening would have eliminated this percentage of the tedious quantitative assays.
Determination of Intracellular Magnesium by an Automatic Titration Procedure
Authors: Sones Donald A , McGuckin Warren F , Wakim Khalil G
Published: January 2020

Our experiences with the automatic titration method of quantitating serum calcium and magnesium are presented. In addition, modifications of the original procedure to allow determination of intraerythrocyte concentrations of magnesium are described.

It appears that adoption of a separate magnesium standard in addition to the calcium standard, plus certain other minor modifications designed to minimize the variables inherent in the procedure, provides a significant increase in accuracy and reproducibility of results.

Values for intraerythrocyte magnesium concentration in 9 normal dogs were found to range from 4.69 to 5.77 mg./100 ml. Values for 4 dogs that received long-term administration of chlorothiazide also fell within this normal range.
Nicotinic Acid Assay in Blood and Urine
Authors: Baker Herman , Frank Oscar , Pasher Inez , Hutner S H , Sobotka Harry
Published: January 2020

Measurement of nicotinic acid activity of blood, serum, and urine by means of the ciliate Tetrahymena pyriformis is described. Blood and urine have high activity; serum has little. Narrow specificity and high sensitivity recommend the assay for clinical use.
Vitamin B12, in Human Blood and Serum
Authors: Baker Herman , Frank Oscar , Pasher Inez , Sobotka Harry
Published: January 2020

A comparison of microbiologic assays for vitamin B12 in whole blood or serum was carried out with four B12-requiring microorganisms, Escherichia coli 113-3, Lactobacillus leichmannii ATCC No. 7839, Euglena gracilis, strain Z, and Ochromonas malhamensis. B12 values in whole blood and serum for normal subjects are given. The value of microbiologic assays is discussed.
A New Approach to Acid-Base Metabolism
Authors: Astrup Poul
Published: January 2020

A technic of high accuracy for determining the acid-base values of blood is based on the equilibration principle. Exact measurement of blood pH allows calculation of all acid-base data. Capillary blood may be used for the determination.
Plasma and Red Cell Cholesterol
Authors: Fels Gordon , Kanabrocki Eugene , Kaplan Ervin
Published: January 2020

The experimental production of hypercholesteremia in rabbits by three independent methods—namely, high-fat feeding, cortisone injection, and Tween-80 injection—results in an elevated plasma total cholesterol, whereas the total RBC cholesterol remains constant. Previous work on plasma and red cell cholesterol in humans has been substantiated. Normal total plasma and red cell cholesterol values are 187 ± 32 and 129 ± 20 mg.%, respectively.

Elevated plasma total cholesterol occurring in coronary arteriosclerosis, diabetes, nephritis, hypothyroid, Hodgkin's disease, and obesity does not affect the erythrocyte levels. Elevated erythrocyte total cholesterol levels occur in sickle cell and pernicious anemia accompanied by slightly sub-normal plasma levels. A hypothesis is advanced to explain the variability of plasma cholesterol and the relative constancy of red cell cholesterol.
Method for the Estimation of Phenothiazine Derivatives in Urine and Blood
Authors: Hetzel Charles A
Published: January 2020

A rapid sensitive method for the estimation of phenothiazine type drugs and their metabolites with an intact thiazine ring in biological fluids is presented. The method is based on the calorimetric determination of the yellow nitration products of these compounds formed after their alkaline ether extraction.
Serum β-Glucuronidase Assay by the Phenolphthalein Mono-β-Glucuronide Method
Authors: Goldstein Gilbert
Published: January 2020

In the phenolphthalein mono-β-glucuronide method for β-glucuronidase assay, diminished enzyme levels have been observed when trichloroacetic acid or heat coagulation are used for deproteinization, but not when acetone is used for this purpose. Data are presented to show the effect of these reagents when blood serum is used as a source of enzyme.

The optimum pH of serum β-glucuronidase was found to be 4.1-4.2 in acetate buffer at 37°, and the assay is performed most conveniently without protein removal.
Some Biochemical Studies in Retinitis Pigmentosa
Authors: Wagreich Harry , Lasky Mortimer A , Elkan Bruno
Published: January 2020

Sixty patients suffering from retinitis pigmentosa were screened by routine clinical laboratory blood determinations. No unusual data were obtained. There was a tendency for the alpha-1 and gamma globulins levels to be high-normal.

Biochemical screening of this type is shown to be nonrevealing for this condition. It is, therefore, desirable to look elsewhere for the cause (or causes) of this condition.
Routine Analysis of Porphyrins in Urine
Authors: Mills Gordon C
Published: January 2020

Procedures are described that utilize an anion exchange resin for preliminary purification of porphyrins from highly colored urine specimens. Following purification, porphyrins may be quantitatively determined by a spectrophotometric method. A procedure is outlined for routine screening of porphyrins in the urines of hospital patients.
Studies on the Determination of Bile Pigments
Authors: Henry Richard J , Jacobs S L , Berkman Sam
Published: January 2020

Several preparations of urobilin and stercobilin were investigated with regard to their value as standards for the determination of urobilinogen and urobilin in biologic specimens. Products of commercial origin were found to be impure and therefore unsuitable for this purpose. Absorptivities were measured for solutions of the pigments in 3% HCI in methanol and for the chromogens, obtained by ferrous hydroxide reduction, in the "quantitative" and "semiquantitative" methods for urobilinogen. Ascorbic acid was shown to be effective as a protective agent in filtrates from reduction mixtures.

Spectra of urobilinogen-aldehyde, phenolsulfonphthalein, Pontacyl dye mixture and phenolphthalein were compared. Phenolsulfonphthalein is recommended as the artificial standard of choice. The independence of this procedure from instrumental considerations, within limits, is demonstrated with the use of this dye.
Automatic Titration with Direct Read-out of Chloride Concentration
Authors: Cotlove Ernest , Nishi Hiroshi H
Published: January 2020

Direct read-out of chloride concentration is provided by an auxiliary designed for use with the automatic coulometric-amperometric titrator of Cotlove et al. (1). The circuitry, construction, and operation of the auxiliary are described. Automatic titration of samples of biologic fluids such as serum, cerebrospinal fluid, urine, sweat, and gastrointestinal fluids requires no prior preparation and the usual titration is completed within 1 min. The chloride concentration of the sample appears on a digital register directly in milliequivalents per liter. In routine use by various technologists in a clinical chemistry laboratory, the auxiliary-titrator combination has proved to be simple to operate and consistently accurate. The procedure requires only 0.1 ml. of solutions containing 10-400 mEq./L. of chloride (or 1 ml. of solutions with lower concentrations down to 1 mEq./L.). Optimal accuracy with a 0.1-ml. sample was in the concentration range above 40 mEq./L., in which the coefficient of variation was about ± 0.5 per cent.
pH Standard for Blood and Other Physiologic Media
Authors: Bower Vincent E , Paabo Maya , Bates Roger G
Published: January 2020

A new National Bureau of Standards pH standard, intended to facilitate measurements of the pH of blood and other physiologic media in the range 7-8, is announced. The new buffer solution is composed of KH2PO4 (0.008695 molal) and Na2HPO4 (0.03043 molal). The standard pH values (pH8) of this solution from 0 to 50° are listed.
Steroid Metabolism and Genetics
Authors: Savard Kenneth
Published: January 2020

Although a clear distinction between anabolic and catabolic processes of steroid metabolism was not made in any of the above studies, the influence of genetic background upon the picture of over-all steroid metabolism can no longer be in doubt. It remains now for future studies to be carried out on normal people, not in their usual role as controls for their less lucky, diseased fellows, but rather as subjects of studies to establish the inherited capacity to elaborate and metabolize characteristic amounts of specific steroid hormones. At the present time, there is no evidence of any pathological significance to such correlations; perhaps all of them will be at a subclinical level. On the other hand, such mild conditions as irregular menses, idiopathic hirsutism, premenstrual tension, all of whose hormonal causes have so far eluded investigators, may well be a reflection of genetic influence causing a slight derangement in the quantitative character of steroid metabolism.
Colorimetric Determination and Distribution of Urinary Creatinine and Creatine
Authors: Clarke John T
Published: January 2020

“Apparent” creatinine and “total” creatinine levels in urine can be estimated to within 2 per cent accuracy by means of the Jaffe colorimetric reaction, provided that certain requirements for the colorimetric reaction itself are met, and provided that appropriate conditions for the conversion of creatine to creatinine are used. The amount of noncreatinine Jaffe-positive material appears to be negligible in most urines, but it can be evaluated with paper chromatography and ion-exchange technics.

More than 88 per cent of normal subjects excrete 300-900 mg. creatinine per 100 lb. of total body weight per day, with the average at 600 mg. Normal males excrete creatinine at an average rate of 875 mg.

Creatine excretion in normal subjects ranges more widely. From 0-800 mg. per 100 pounds of total body weight per day is excreted (as. creatinine), with the average at 275 mg., regardless of sex or age.

Certain malabsorption syndromes (cystic fibrosis and celiac disease) include distinct creatinurias.
The Interaction of Nonionic Detergents with Protein in Paper Electrophoresis
Authors: Dowben Robert M , Koehler Walter R , Barrieux Genevieve
Published: January 2020

Addition of polyoxyethylene nonionic detergents to the buffer in paper electrophoresis results in alteration of the rate of migration and shape of protein peaks. At low detergent concentrations, disruption of paper-protein binding leads to faster migration and sharper peaks. At high detergent concentrations, interaction of detergent with protein leads to slower migration and broader peaks. On glass-fiber paper, which binds protein less strongly than ordinary cellulose filter paper, only slowing of migration occurs upon addition of detergent to the buffer. Electrophoresis of polysaccharides using buffer-containing detergent results only in a slight increase in migration.
Interference—free Flame Photometry of Calcium in Serum and Urine
Authors: Thiers Ralph E , Hviid Kirsten
Published: January 2020

Data are given for the rapid determination of calcium in biologic material by flame photometry. An "automatic background-subtraction," photometer added to the available instrumentation eliminated cation interference, while the use of a chelating agent (EDTA) prevented interference from anions (chiefly phosphate). The procedure shows excellent precision and accuracy in comparison with standard chemical procedures and in the analysis of control sera.
Critique of the Determination of Proteins in Cerebrospinal Fluid
Authors: Rice Eugene W , Loftis John W
Published: January 2020

Cerebrospinal fluid protein values obtained by the biuret procedure of Goa or the TCA-turbidimetric method of Meulemans are shown to be comparable to those obtained by the more involved tyrosine-equivalence "reference" method of Johnston and Gibson. Both of the former methods are recommended for routine use because of their accuracy and simplicity.
An Evaluation of Serum "Trypsin" Tests
Authors: Babson Arthur L , Read Williams Prunella A , Phillips George E
Published: January 2020

When crystalline trypsin was dissolved at various concentrations in pooled serum, the rates of hydrolysis of α-benzoyl-1-arginineamide (BAA) and N-α-benzoyl-dl-arginine-β-naphthylamide (BANA) were not linear functions of the trypsin concentration. Also, the plot of trypsin activity in relation to trypsin concentration differed with different sera. The apparent tryptic activity toward these substrates is felt to be a function of the concentration of serum trypsin inhibitor and, with BANA only, some unidentifed proenzyme which is activated by trypsin. Therefore, it is concluded that it is not feasible to measure serum trypsin concentration with these substrates.
A Graphic Prothrombin Time Recorder with Air Bath
Authors: Hamilton Robert Houston
Published: January 2020

An air bath is described which maintains plasma, reagents, and glassware at constant temperature. Within this bath is a variable light source, without filters, from which light passes through the liquid mixture of plasma and reagents (0.3-ml. volume) to a photoelectric cell. The output of the cell is fed into a Speedomax recorder. Addition of reagents and time of clotting show clearly on the record, and specimens can be run through the instrument at the rate of one to two per minute. Prothrombin time is determined by measurement between points on the recorded curves.

The instrument has been in continuous use at Temple University Medical Center since 1953. Prothrombin contents check well with those obtained visually in a constant-temperature room. Technologists regard use of the instrument as less fatiguing than the visual method. Results are perhaps more objective.
Modified Reagents for Determination of Urea and Ammonia
Authors: Chaney Albert L , Marbach Edward P
Published: January 2020

Combinations of reagents are described for the catalyzed indophenol reaction for the determination of ammonia, which produces a stable blue color. The procedure is adapted to the determination of urea after hydrolysis with urease.
Optimal Conditions for the Enzymatic Determination of L-Lactic Acid
Authors: Olson G F
Published: January 2020

An additional end-point method for the enzymatic measurement of lactic acid has been described by G. Gercken in Hoppe-Seyler's Zeitschrift fur physiologische Chemie (Bd. 320 S. 180-186, 1960) : By employing an As2O3-NaOH buffer containing 2.5 x 10-3 M hydrazine, Gercken has largely eliminated changes in blank values and the backoxidation of reduced DPNH.

References 5 and 8 should be "Biochem. Z.," not "Biochem. J."
Observations on the Zak Cholesterol Reaction: Glacial Acetic Acid Purity, a More Sensitive Absorbance Peak, and Bromide Enhancement
Authors: Bowman Robert E , Wolf Richard C
Published: January 2020

An examination of the absorbance spectrum of the Zak cholesterol reaction, made with two brands of commercially available reagent-grade glacial acetic acid, showed not only the expected peak at 560 mµ, but an additional, higher peak at about 490 mµ. A specially purified glacial acetic acid did not show this 490 mµ peak. Conversely, increasing the ratio of color reagent to glacial acetic acid from 0.8 to 1.2 (v/v) greatly increased the height of the absorbance peak at 480 mµ and eliminated the 560 mµ peak. Under optimum conditions of time and color-reagent concentrations, the 480 mµ peak affords approximately double the sensitivity for cholesterol as compared to the 560 mµ peak. Finally, it was observed that the reported interference of bromide and iodide ions in the Zak reaction results almost entirely from an enhancement effect on the color by the cholesterol itself, and that the addition of about 100 µg. NaBr per milliliter of glacial acetic acid prior to reaction produced the full enhancement of 50 per cent greater color, and virtually eliminated interference at 560 mµ from additional amounts of bromide or iodide salts.
A Rapid and Specific Ultramicro Method for Total Serum Cholesterol
Authors: Bowman Robert E , Wolf Richard C
Published: January 2020

A modification of the Zak cholesterol reaction is described in which ethanol is substituted for glacial acetic acid. This modification avoids the hazard of purifying glacial acetic acid and also increases the specificity of the reaction by eliminating interference from bromide or iodide salts. The ethanolic reaction has the absorbance spectrum, sensitivity, and stability of the usual acetic acid reaction.

A rapid ultramicro method has been developed based on this ethanolic reaction. A 0.01- to 0.05-ml. sample of serum is extracted with 2.5 ml. of ethanol, and a 2.0-ml. aliquot of this extract is reacted directly with 2.0 ml. of a Zak color reagent. Cholesterol concentrations as determined by this procedure and by the Sperry-Webb method showed satisfactory agreement for monkey and human sera, including normal, hemolyzed, high cholesterol, and severely lipemic or jaundiced sera..
A Convenient Apparatus For Vertical Gel Electrophoresis
Authors: Raymond Samuel
Published: January 2020

An apparatus is described incorporating gel mold, electrode chambers, and direct-contact cooling plates. It eliminates several steps in preparing and handling the gel, and permits use of either rigid (starch) of flexible (acrylamide) gels. Electrophoretic analyses can be completed in 2-4 hr. Examples are given of serum and hemoglobin electrophoretic patterns obtained.
A Study of the Thymol Turbidity Test with Special Reference to Buffer Behavior
Authors: Reinhold John G
Published: January 2020

Replacement of barbiturate buffer by a tris-hydroxymethylaminomethane buffer in the thymol test reagent of Maclagan greatly improves the stability of the reagent. Thymol turbidity measurements made by means of the modified reagent agreed closely with those made with barbiturate-containing reagents. However in hyperlipemic sera, the latter reagent gave higher turbidities. A reaction of barbiturate with serum chylomicrons and triglycerides explains the difference.

It is believed that the modified reagent is less likely to be affected by casual changes in serum lipid concentration and that therefore it should prove to be more dependable as an aid in the study of liver disease.

Heating is not an essential operation in preparation of thymol test reagents.

The pH is of critical importance in measurement of thymol turbidity. The large change in pH of barbiturate and Tris buffers with change in temperature makes careful control of temperature essential. Tables showing the appropriate reagent pH at various laboratory temperatures are presented.
Logarithmic Recording Spectrophotometer for Densitometry and Flow Spectrophotometry
Authors: Zak Bennie , Holland Jack , Williams Louis A
Published: January 2020

A system is described for the conversion of a Beckman DU spectrophotometer to automatic recording-integrated densitometry. This system has also been applied to flow spectrophotometry with a wide-range monochromatic system substituted for the filter photometer of the Technic on AutoAnalyzer. A log converter is used which changes the impulse from linear to logarithmic and feeds this to the recorder. The converter can also be used in conjunction with the multirange control of the recorder to vary the recorded sensitivity of the spectrophotometric system; this represents a great increase in versatility to the investigator. Several applications of the instrumentation are described.
Serum Factors Causing Abnormal Retardation of the Microelectrophoretic Mobility of the Red Blood Cell During Disease
Authors: Rottino Antonio , Angers John
Published: January 2020

Erythrocytes of healthy humans migrate at a constant mobility in an electric field. This mobility is retarded in a variety of nonmalignant diseases and almost invariably in malignant neoplasm.

The serum of healthy persons contains a factor that will restore normal mobility to cells with retarded mobility. The serum from both malignant neoplasm and nonmalignant disease contains a factor that will retard the mobility of normally-migrating cells.

The factor in the serum of malignant neoplastic disease can be differentiated from the factor in the serum of nonmalignant disease.
Changes in Ammonia Values of Protein-free Filtrates of Blood During Storage in the Frozen State
Authors: Wilder Charles E
Published: January 2020

Protein-free filtrates of blood treated with trichloracetic acid were divided into two or three parts. The ammonia concentration of one of these was determined immediately by the ninhydrin method described by Nathan and Rodkey (1). The others were kept frozen for periods of 1-8 days and then thawed and analyzed. The blood ammonia concentrations calculated from these filtrate values were compared. A significant change in ammonia level during frozen storage was demonstrated.
Microdetermination of Cholesterol and Phospholipid in Cerebrospinal Fluid and Serum by Silicic Acid Column Chromatography
Authors: Shin Yung S , Lee James C
Published: January 2020

A method is presented for the determination of cholesterol and phospholipid, which requires 5 µl. of human serum or 1-2 ml. of cerebrospinal fluids. With this method 5-100 µg. of cholesterol and phospholipid can be separated by a modified silicic acid column after elution of the mixture with 1 ml. of chloroform and 3 ml. of methanol. Recovery for 24.6 µg. of cholesterol and 30.5 µg. of phospholipid was 98.4 and 96.7%, respectively. Standard deviations of ± 1.73 and ± 1.24 have been obtained for the reproducibility of cholesterol and phospholipid determinations after chromatography. The method has been applied for the estimation of the cholesterol/phospholipid ratio and of lipid phosphorus in total phosphorus of human cerebrospinal fluids.
Estimation of Low-Density Lipoprotein Immunoprecipitates in Uniform Drops of Serum
Authors: Searcy R L , Asher T M , Bergquist L M
Published: January 2020

An immunochemical technic has been found to be specific, efficient and reproducible in removing lipoproteins of density less than 1.063 gm./ml. from measured drops of human serum. Estimations of microcapillary columns of immunoprecipitate compare favorably with ultracentrifugal analysis of Sf 0-400 lipoproteins. An equation derived from these data converts millimeters of lipoprotein precipitate into milligrams lipoprotein Sf 0-400 per 100 ml. serum. A highly significant difference was obtained between mean lipoprotein precipitate levels of a clinically healthy population and those of a group of patients with coronary artery disease or diabetes mellitus.
Variations in Levels of Transaminases and Lactic Dehydrogenase in Bank Blood
Authors: Crowley Leonard V
Published: January 2020

Results of the assay of transaminases and lactic dehydrogenase in blood, proposed as a screening procedure for subclinical hepatitis in blood donors, show that the method of sampling influences the analytic results. Determinations of GOT and GPT may prove useful if made on specimens separated from cells soon after collection. Plasma in contact with cells from blood preserved in acid citrate dextrose solution appears to yield good results up to 21 days. Lactic-dehydrogenase levels are of limited value for this screening.
Oxidation of Homogentisic Acid by Nitrous Acid and its Interference in the Determination of 5-Hydroxyindoleacetic Acid
Authors: Davis Richard B
Published: January 2020

Oxidation of homogentisic acid to the corresponding quinone occurs in the presence of reagents used to develop the violet chromophore with 5-hydroxyindoleacetic acid(5-HIAA). With amounts of homogentisic acid well below those excreted in alkaptonuria, significant interference in the development of the violet chromophore of 5-HIAA occurs. The mechanism of this interference is discussed. Compounds related to homogentisic acid do not cause interference. Using the simple conditions described, a rapid oxidation of homogentisic acid is effected. Absorption of the corresponding quinone is stable and linear with relation to the initial concentration of homogentisic acid over a 10-fold range of concentration.
A New Simple Semimicro Method for Colorimetric Determination of Urea
Authors: Coulombe J J , Favreau L
Published: January 2020

A new simple and rapid method for quantitative semimicro determination of blood urea is presented. Diacetyl monoxime and thiosemicarbazide form in acid medium with urea a red color complex with a maximum adsorption at 530 mµ stable at room temperature and requiring 0.2 ml. of 1:10 blood filtrate.
Determination of Serum Amino Acids
Authors: Rapp Robert D
Published: January 2020

The reaction of 1-fluoro-2,4 dinitrobenzene with amino acids was investigated as an assay procedure for serum amino acids. An aliquot of a tungistic acid filtrate of serum is buffered at H 10, mixed with the buffered reagent, and heated at 56° for 15 min. The resultant color is read at 420 mµ.
Extraction Procedure for the Measurement of Blood Volume with Brilliant Vital Red
Authors: Takeda Y
Published: January 2020

A simple extraction method usable for Brilliant Vital Red is described. The dye is displaced from its combination with albumin by detergent, adsorbed on a cotton cellulose column, and eluted with 40% acetone-water at pH 8.0. Recovery of Brilliant Vital Red from plasma averaged 95%. Measurements are not affected when the plasma samples are hemolyzed, jaundiced, or lipemic, or when dextran is present. Patients therefore require no previous preparation. Simultaneous measurements of blood volume were made by Brilliant Vital Red and l131-albumin in 17 patients. The results of the two methods were in close agreement.
A Simplified Method for Determination of Urinary Lead
Authors: Hilf Russell , Castano Frank F
Published: January 2020

A modification for simplifying the quantitative determination of urinary lead by reaction with dithizone is described. The detailed procedure is presented and data on recoveries are given. The method takes less time than the original procedure with no loss in accuracy.
Clot Retraction and Fibrinolysis
Authors: Weiner Murray
Published: January 2020

Three different systems were employed for parallel observations of clot lysis and retraction. Potassium and calcium concentration was found to influence significantly these phenomena in some systems but not in others. Under a variety of conditions, both retraction and fibrinolysis are affected in a parallel manner, suggesting that the retraction state of a clot used as a substrate may influence the apparent fibrinolytic activity of an enzyme system.
Variation in Excretion of Certain Amino Acids With Age
Authors: Stambaugh R , Davidson D T , Elkinton J R
Published: January 2020

By relating amino acid excretion to creatinine excretion in a specimen of urine from fasting patients, the normal variation of cystine, glutamine, glycine, and alanine excretion in relation to creatinine excretion and the age of the individual has been defined. No amino acid excretion differences between the two sexes were detectable. In general, the excretion levels for these four amino acids were found to be highest in infancy and decreased markedly with age. However, this decrease is not a uniform or gradual one. The greatest decrease occurs between the 3-5-year and 6-8-year groups, and the excretion levels again increase slightly between the 9-11-year and 12-14-year groups.
Quantitative Gravimetric Fractionation of Brain Tissue
Authors: Sperry Warren M
Published: January 2020

With the procedure which is described, brain tissue is separated into six fractions, the sum of whose weights equals the dry weight of the tissue. Three of these primary fractions are further separated into subfractions. Recovery is quantitative at each step. The procedure, as applied to rat brain, gave consistent results; duplicate analyses of the two halves of brains, divided as equally as possible along the anteroposterior line, agreed closely, and the variation from rat to rat in the percentages of the various fractions in dry tissue was small, as illustrated by the following results: main lipid fraction, 40.65 ± 1.03 (S.D.)%; protein residue, 44.45 ± 0.87%; water-soluble fraction from Folch purification, 5.94 ± 0.23%; crude "strandin" fraction, 1.25 ± 0.05%. The average percentage of dry in fresh tissue was 24.87 ± 0.41. The method includes procedures for the separation of a fraction, obtained by treatment with acidified chloroform-methanol, into four well-defined fractions, of which one is characterized by extreme surface activity in aqueous solution. A small amount of lipid is so firmly bound in brain tissue as to resist extraction during exhaustive treatment with chloroform-methanol (2:1), acidifed chloroform-methanol, and acetone. Significant radioactivity was present in most of the fractions from the brains of rats which had received a peritoneal injection of acetate-C14 5-15 months previously during the period of early development.
Factitiously Low Amylase Values
Authors: Sax Sylvan M , Trimble George E
Published: January 2020

When a commercial substrate was used in the determination of serum amylase activities of patients with acute pancreatitis, results much higher than those reported by the manufacturer with similar patients were found. A failure to quantitate all of the reducing groups liberated during incubation may account for the lower results. A modified saccharogenic method has been developed, which, by increasing the ratios of starch to enzyme and copper to reducing sugars, considerably extends the range of the determination. Unequivocally elevated serum and urine amylase values can be measured without repetition of all or part of the test and with good precision.
Barbiturate Detection using Thin-layer Chromatography
Authors: Sunshine Irving , Rose Eleanor , LeBeau Jack
Published: January 2020

Thin-layer chromatography has been applied to the analysis of barbituric acids. The ratio of the Rf of 23 different barbituric acid samples to that of simultaneously run phenobarbital is given. This ratio is reproducible and characteristic. By using this technic the average laboratory can provide a barbiturate analysis of biologic material in about 2 hr.
Plasma and Erythrocyte Enzymes in Phenylhydrazine Anemia
Authors: Friedman Max M , Lapan Bernard , Kahn Bernard S
Published: January 2020

Dehydrogenases and transaminases occur in high activities in the erythrocyte when compared to the plasma in which the erythrocyte is suspended. Destruction of the erythrocyte with phenylhydrazine does not release any enzyme activity into the plasma.
Serum Lactic Dehydrogenase Activity: An Analytical Assessment of Current Assays
Authors: Amador Elias , Dorfman Lionel E , Wacker Warren E C
Published: January 2020

Serum LDH activities assayed spectrophotometrically by the "forward" (lactate + DPN to pyruvate + DPNH + H) method have linear reaction rates, activity proportional to the amount of serum added, and a reproducibility of 1.3%. The reagent mixture can be stored frozen for 6 months and in the lyophilized state indefinitely.

Poor separation of normal from abnormal serum LDH activities results from the nonlinear calibration curves and decreasing reaction rates of the "backward" spectro-photometric assay. The dinitrophenylhydrazine colorimetric assay is deemed unsuitable for clinical use because large variations in activity result from minor variations in the reagent calibration curve, and because colorimetric activities are inaccurate as compared to activities obtained with the "forward" spectrophotometric assay.
The Effect of Chemotherapeutic Agents upon the Metabolism of Intact Human Cancer Cells
Authors: Katchman Bernard J , Zipf Robert E , Murphy James P F
Published: January 2020

The effect of certain chemotherapeutic agents upon the metabolism of human ascites and leukemic leukocytes was investigated. Human leukemic blast cells show 2-3 times the respiratory activity of "chronic" cells. From a study of the effects of eight chemotherapeutic drugs upon the respiration of human leukemic leukocytes and human ascites cells, relative index of cell sensitivity was obtained.

The alkaloid, vinblastine sulfate, and the alkylating agents, triethylenethiophosphoramide and nitrogen mustard, were found to be more toxic to human cancer cells than the antimetabolites, 6-mercaptopurine, 8-azaguanine, aminopterin, diazouracil, or prednisone. Stimulation of aerobic glycolysis was found for all chemicals except aminopterin (no effect) and nitrogen mustard (inhibition).

No correlation between stimulation of lactic acid production and inhibition of respiration was found. Stimulation of lactic acid production could be produced under conditions where respiration was unchanged. Only nitrogen mustard differed in that inhibition of respiration always accompanied inhibition of lactic acid production.

Most chemotherapeutic agents tested are Pasteur effect inhibitors.

An unusual stimulation of glucose disappearance to products unknown as yet was caused by 6-mercaptopurine in all cells tested. The potential usefulness of a cell sensitivity test in clinical chemotherapy is discussed.
Use of a Lyophilized Serum Enzyme Preparation in Quality Control
Authors: Hersey Melford Q , Hartwell Katherine , Doe Richard P
Published: January 2020

A purified preparation of alkaline phosphatase added to standardized lyophilized serum has been used by the Minneapolis Veterans Administration Reference Laboratory to evaluate the routine alkaline phosphatase method in use in the 10 laboratories in its reference area.

Evidence of a marked need for investigation of the routine method for alkaline phosphatase determination was found in 3 of the 10 laboratories.

A semiquantitative phosphatase method proved to be useful as an independent procedure for use in evaluation of the different laboratories.
Metabolic Disorders Leading to Mental Deficiency
Authors: Karlsson J L
Published: January 2020

A new approach is described for the detection of abnormal metabolites in the urine of patients with known or suspected metabolic disorders. Distribution curves are presented for nonurea organic carbon and nitrogen which form a basis for judging whether grossly abnormal amounts of organic materials are present in the urine.

Families with recurrent mental retardation have been identified whose mental defect may be on an unknown metabolic basis.
Micromethod for Estimation of Serum Adenosine Deaminase
Authors: Martinek Robert G
Published: January 2020

A micromethod is described for assessing adenosine deaminase activity in serum. Its greater simplicity recommends it for routine use in the clinical chemistry laboratory. Comparison is made with a previous method described in this Journal. No clinical appraisal was made.
A Rabbit Serum Calcium Lowering Factor from the Pituitary
Authors: Natelson Samuel , Pincus Joseph B , Rannazzisi Gandolfo
Published: January 2020

A factor has been shown to exist in ACTH fractions of porcine pituitaries which lowers serum calcium levels markedly when injected intramuscularly in the fasting rabbit. The lowest value is usually reached in 1.5-2.5 hr. and returns to normal in 5-6 hr.

It has been demonstrated that the activity of this material is independent of the ACTH activity of the preparation and is distinct from the pituitary hormones TSH, LTH, STH, or oxytocin. This factor can lower serum calcium levels in rabbits to as low as 50% of its initial value, producing tetany and convulsions.

It has also been demonstrated that the action of this material is not mediated through the release of 1-adrenaline, 1-noradrenaline, insulin, glucagon, ascorbic acid, cortisone, hydrocortisone, or corticosterone, all of which substances are without significant effect. Parathormone raises serum calcium levels slowly in the rabbit. Commercial vasopressin preparations are active in lowering serum calcium levels but not to as low a level as the ACTH preparations.

It has also been demonstrated that under stress the rabbit's serum calcium is spontaneously lowered to a slight degrree (10%).
The Renal Clearance of Sodium Pentaborate in Mice and Men
Authors: Farr Lee E , Konikowski T
Published: January 2020

The renal blood clearance of sodium pentaborate was observed in 8 patients undergoing neutron capture therapy for intracranial malignant tumors and was found to average 39.1 ml./min. per 1.73 sq. m. surface area.

The renal blood clearance was calculated for mice receiving sodium pentaborate intravenously in dosages of 25 µ.g./gm. body weight and 100 µg./gm., calculated as boron. The average clearance for the mice receiving the larger dose was 0.207 ml./min. for a 21-gm. mouse. The average clearance for the mice receiving the smaller dose was 0.192 ml./min. per 21-gm. mouse.

For the mouse, clearance calculated for a surface area of 1.73 sq. m., as was used in man, averages 40 ml./min.

No toxic effects on renal function were observed in mice at the higher dosage.
Competition Between Calcium, Strontium, and Magnesium for Absorption in the Isolated Rat Intestine
Authors: Hendrix J Z , Alcock N W , Archibald R M
Published: January 2020

Rats 1-2 mo. old were placed on a low calcium or a low calcium and low magnesium diet. Absorption in isolated rat intestine was studied in vitro. Duodenal segments which actively took up and actively transported Ca45++ well, actively took up and actively transported Sr85++ well; where Ca45++ active uptake and active transport was poor, that of Sr85++ was low. The uptakes of Ca45++, Sr85++, and Mg28++ by the gut tissue were greater than the amounts transported. Ca++, Sr++, and Mg++ decreased the active uptake of Ca45++ and Sr85++ by the duodenum. Ca++ decreased the rate of active transport to the serosal media of Ca40++ and Sr85++. Ca++ was more effective in decreasing the active uptake of Sr55++ than was Sr++. The active uptake of Ca45++ by the ileum was reduced by Mg++ and Sr++. The active uptake of Mg28++ by the ileum was reduced by Ca++. The rate at which Mg28++ crosses and is taken up by the small intestine increases as one progresses from the proximal duodenum to the distal ileum. Ca++ was actively transported by the colon. Ca++, Sr++, and Mg++ appear to share a common pathway for absorption by the gut, but in the various areas of the intestine the rate of absorption of a particular divalent cation and the degree of competition between the divalent cations varies. Therefore, the absorption of a particular cation may involve also other pathways.
Sequencing Analysis of Plasma Epstein-Barr Virus DNA Reveals Nasopharyngeal Carcinoma-Associated Single Nucleotide Variant Profiles
Authors: Lam W K Jacky , Ji Lu , Tse O Y Olivia , Cheng Suk Hang , Jiang Peiyong , Lee P H Patrick , Lin S Vivien , Hui Edwin P , Ma Brigette B Y , Chan Anthony T C , Chan K C Allen , Chiu Rossa W K , Lo Y M Dennis
Published: January 2020

Background

Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. Plasma EBV DNA is a validated screening tool for NPC. In screening, there are some individuals who do not have NPC but carry EBV DNA in plasma. Currently it is not known from screening if there may be any genotypic differences in EBV isolates from NPC and non-NPC subjects. Also, low concentrations of EBV DNA in plasma could pose challenge to such EBV genotypic analysis through plasma DNA sequencing.

Methods

In a training dataset comprised of plasma DNA sequencing data of NPC and non-NPC subjects, we studied the difference in the EBV single nucleotide variant (SNV) profiles between the two groups. The most differentiating SNVs across the EBV genome were identified. We proposed an NPC risk score to be derived from the genotypic patterns over these SNV sites. We subsequently analyzed the NPC risk scores in a testing set.

Results

A total of 661 significant SNVs across the EBV genome were identified from the training set. In the testing set, NPC plasma samples were shown to have high NPC risk scores, which suggested the presence of NPC-associated EBV SNV profiles. Among the non-NPC samples, there was a wide range of NPC risk scores. These results support the presence of diverse SNV profiles of EBV isolates from non-NPC subjects.

Conclusion

EBV genotypic analysis is feasible through plasma DNA sequencing. The NPC risk score may be used to inform the cancer risk based on the EBV genome-wide SNV profile.
GLEE: Geometric Laplacian Eigenmap Embedding
Authors: Torres Leo , Chan Kevin S , Eliassi-Rad Tina
Published: January 2020

Graph embedding seeks to build a low-dimensional representation of a graph $G$. This low-dimensional representation is then used for various downstream tasks. One popular approach is Laplacian Eigenmaps (LE), which constructs a graph embedding based on the spectral properties of the Laplacian matrix of $G$. The intuition behind it, and many other embedding techniques, is that the embedding of a graph must respect node similarity: similar nodes must have embeddings that are close to one another. Here, we dispose of this distance-minimization assumption. Instead, we use the Laplacian matrix to find an embedding with geometric properties instead of spectral ones, by leveraging the so-called simplex geometry of $G$. We introduce a new approach, Geometric Laplacian Eigenmap Embedding, and demonstrate that it outperforms various other techniques (including LE) in the tasks of graph reconstruction and link prediction.
MTMR4 SNVs modulate ion channel degradation and clinical severity in congenital long QT syndrome: insights in the mechanism of action of protective modifier genes
Authors: Lee Yee-Ki , Sala Luca , Mura Manuela , Rocchetti Marcella , Pedrazzini Matteo , Ran Xinru , Mak Timothy S H , Crotti Lia , Sham Pak C , Torre Eleonora , Zaza Antonio , Schwartz Peter J , Tse Hung-Fat , Gnecchi Massimiliano
Published: January 2020

Aims

In long QT syndrome (LQTS) patients, modifier genes modulate the arrhythmic risk associated with a disease-causing mutation. Their recognition can improve risk stratification and clinical management, but their discovery represents a challenge. We tested whether a cellular-driven approach could help to identify new modifier genes and especially their mechanism of action.

Methods and results

We generated human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) from two patients carrying the same KCNQ1-Y111C mutation, but presenting opposite clinical phenotypes. We showed that the phenotype of the iPSC-CMs derived from the symptomatic patient is due to impaired trafficking and increased degradation of the mutant KCNQ1 and wild-type human ether-a-go-go-related gene. In the iPSC-CMs of the asymptomatic (AS) patient, the activity of an E3 ubiquitin-protein ligase (Nedd4L) involved in channel protein degradation was reduced and resulted in a decreased arrhythmogenic substrate. Two single-nucleotide variants (SNVs) on the Myotubularin-related protein 4 (MTMR4) gene, an interactor of Nedd4L, were identified by whole-exome sequencing as potential contributors to decreased Nedd4L activity. Correction of these SNVs by CRISPR/Cas9 unmasked the LQTS phenotype in AS cells. Importantly, the same MTMR4 variants were present in 77% of AS Y111C mutation carriers of a separate cohort. Thus, genetically mediated interference with Nedd4L activation seems associated with protective effects.

Conclusion

Our finding represents the first demonstration of the cellular mechanism of action of a protective modifier gene in LQTS. It provides new clues for advanced risk stratification and paves the way for the design of new therapies targeting this specific molecular pathway.