bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYLD is a causative gene for frontotemporal dementia – amyotrophic lateral sclerosis
Authors: Dobson-Stone Carol , Hallupp Marianne , Shahheydari Hamideh , Ragagnin Audrey M G , Chatterton Zac , Carew-Jones Francine , Shepherd Claire E , Stefen Holly , Paric Esmeralda , Fath Thomas , Thompson Elizabeth M , Blumbergs Peter , Short Cathy L , Field Colin D , Panegyres Peter K , Hecker Jane , Nicholson Garth , Shaw Alex D , Fullerton Janice M , Luty Agnes A , Schofield Peter R , Brooks William S , Rajan Neil , Bennett Mark F , Bahlo Melanie , Shankaracharya  , Landers John E , Piguet Olivier , Hodges John R , Halliday Glenda M , Topp Simon D , Smith Bradley N , Shaw Christopher E , McCann Emily , Fifita Jennifer A , Williams Kelly L , Atkin Julie D , Blair Ian P , Kwok John B 
Published: February 2020

AbstractFrontotemporal dementia and amyotrophic lateral sclerosis are clinically and pathologically overlapping disorders with shared genetic causes. We previously identified a disease locus on chromosome 16p12.1-q12.2 with genome-wide significant linkage in a large European Australian family with autosomal dominant inheritance of frontotemporal dementia and amyotrophic lateral sclerosis and no mutation in known amyotrophic lateral sclerosis or dementia genes. Here we demonstrate the segregation of a novel missense variant in CYLD (c.2155A&gt;G, p.M719V) within the linkage region as the genetic cause of disease in this family. Immunohistochemical analysis of brain tissue from two CYLD p.M719V mutation carriers showed widespread glial CYLD immunoreactivity. Primary mouse neurons transfected with CYLDM719V exhibited increased cytoplasmic localization of TDP-43 and shortened axons. CYLD encodes a lysine 63 deubiquitinase and CYLD cutaneous syndrome, a skin tumour disorder, is caused by mutations that lead to reduced deubiquitinase activity. In contrast with CYLD cutaneous syndrome-causative mutations, CYLDM719V exhibited significantly increased lysine 63 deubiquitinase activity relative to the wild-type enzyme (paired Wilcoxon signed-rank test P = 0.005). Overexpression of CYLDM719V in HEK293 cells led to more potent inhibition of the cell signalling molecule NF-κB and impairment of autophagosome fusion to lysosomes, a key process in autophagy. Although CYLD mutations appear to be rare, CYLD’s interaction with at least three other proteins encoded by frontotemporal dementia and/or amyotrophic lateral sclerosis genes (TBK1, OPTN and SQSTM1) suggests that it may play a central role in the pathogenesis of these disorders. Mutations in several frontotemporal dementia and amyotrophic lateral sclerosis genes, including TBK1, OPTN and SQSTM1, result in a loss of autophagy function. We show here that increased CYLD activity also reduces autophagy function, highlighting the importance of autophagy regulation in the pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
Immunoglobulins in cerebrospinal fluid in various neurologic disorders.
Authors: Bouloukos A , Lekakis J , Michael J , Kalofoutis A 
Published: February 2020

Abstract
We determined the concentrations of immunoglobulins A, G, and M in cerebrospinal fluid of 16 patients suffering from multiple sclerosis, 13 with non-bacterial meningitis, 10 with stroke syndrome, and 13 with epilepsy. The differences in concentrations of immunoglobulins in these groups were remarkable in the patients with multiple sclerosis, meningitis, or stroke syndrome. We propose that the determination of the absolute immunoglobulin content in cerebrospinal fluid is of greater significance than the relative immunoglobulin concentration.
Evaluation of a radioenzymic kit for determination of plasma catecholamines.
Authors: Tasseron S J , Fiolet J W , Willebrands A F 
Published: February 2020

Abstract
We evaluated a commercially available reagent test-kit (Upjohn) for simultaneously determining norepinephrine, epinephrine, and dopamine in 50-microL of plasma. The three catecholamines are enzymically converted into the radioactive O-methyl derivatives and separated by thin-layer chromatography. Day-to-day precision (CV) was 11, 10, and 14% for norepinephrine, epinephrine, and dopamine, respectively. The relationship between concentration of catecholamine and radioactivity (net dpm) was linear to at least 8 ng (corresponding to 1 mumol/L in plasma). Sensitivity was approximately 2 pg for dopamine, 1 pg for each of the other two catecholamines. Under our conditions, epinephrine was not quite completely resolved from the other two fractions. Catecholamine values determined in normal humans, after 30 min supine and after normal laboratory activity, agreed well with those found by other investigators. Correlation was good between kit results and those obtained in another laboratory that used self-prepared reagents and "high-performance" liquid chromatography for the separation.
Continuous-flow analysis for glucose in serum, with use of hexokinase and glucose-6-phosphate dehydrogenase co-immobilized in tubular form.
Authors: León L P , Chu D K , Snyder L R , Horváth C 
Published: February 2020

Abstract
Hexokinase and glucose-6-phosphate dehydrogenase, co-immobilized at the inner wall of plastic tubing, were used with continuous-flow analyzers to measure serum glucose. The performance of the enzyme-containing coils meets the hydraulic requirements of the continuous-flow instruments, and the average carryover does not exceed 2.2%. A glucose concentration change of 1 g/L yields a 0.08 change in absorbance. There is no significant deviation from linearity for glucose concentrations up to 5 g/L. The method is similar to the Reference Method proposed by the Food and Drug Administration, and results by the two methods agree and correlate well (r = 0.999). The operational stability of the enzyme tubes is sufficient to allow the analysis of at least 10 000 serum samples. We investigated in detail the effect of reagent concentrations and temperature on the performance of the enzyme coils, and the results shed light on the nature of the heterogeneous dual-enzymic reaction.
Improved radiochemical method for measuring ferrochelatase activity.
Authors: Williams H L , Johnson D J , Haut M J , Slater S , Brennan R G , Altstatt L B 
Published: February 2020

Abstract
We describe a radiochemical method for measuring ferrochelatase activity in the in vitro incorporation of iron into mesoporphyrin-IX to form mesoheme. 59Fe is used to quantify ferrochelatase activity in rat liver. The uptake of iron is linearly related to the time allowed for it to occur, and the reaction proceeds optimally under reducing and anerobic conditions, maintained in sealed lyophilization vials under a positive pressure of nitrogen.
Mechanism of interference by hemoglobin in the determination of total bilirubin. II. Method of Jendrassik-Grof.
Authors: Shull B C , Lees H , Li P K 
Published: February 2020

Abstract
Oxyhemoglobin in erythrocyte hemolysates interferes with the Jendrassik-Grof assay. Destruction of azobilirubin occurs when oxyhemoglobin is oxidized to methemoglobin during diazotization or to alkaline hematin with addition of alkaline tartrate. The most probable mechanism is by oxidation with an agent such as hydrogen peroxide or a related species resulting from hemoglobin oxidation. Methemoglobin also appears to cause some destruction of azobilirubin during diazotization. Methemoglobin forms during diazotization because of reactions of oxyhemoglobin with both diazo reagent and nitrite ion. Formation of methemoglobin is, therefore, more rapid in the test than in the blank mixture and, under reaction conditions, its absorbance is less than that of oxyhemoglobin. This results in spectral interference when neutral azobilirubin is assayed. Alkaline tartrate abolishes this spectral error by causing rapid formation of alkaline hematin in both test and blank.
A fluorometric determination of sphingomyelinase by use of fluorescent derivatives of sphingomyelin, and its application to diagnosis of Niemann-Pick disease.
Authors: Gatt S , Dinur T , Barenholz Y 
Published: February 2020

Abstract
We synthesized fluorescent derivatives of sphingomyelin (N-acyl-sphingosylphosphocholine) and used them as substrates for several sphingomyelinases. The following five fluorescent probes, each attached to the terminal carbon atom of the fatty acyl residue, were introduced into sphingomyelin: dansyl, pyrene, carbazole, 4-chloro-7-nitrobenz-2-oxa-1,3-diazole, and anthroic acid. We compared the rates at which the fluoro- and radiolabeled sphingomyelins were hydrolyzed. They were the same with the following three spingomyelinases: (a) a purified enzyme from Staphylococcus aureus; (b) at Triton X100-treated extract of human brain (assayed at pH 7.4 in the presence of Mg2+; and (c) aqueous extracts of brain lysosomes, skin fibroblasts, and amniotic cells, assayed at pH 5.0. Homogenates of skin fibroblasts of a patient with Niemann-Pick disease had practically no activity when assayed at pH 5, with fluorosphingomyelin as substrate. When fluorosphingomyelin was mixed in various proportions with natural sphingomyelin, enzymes from each of the three sources hydrolyzed the two substrates at equal rates. The fluorosphingomyelins can be used to estimate with great sensitivity the sphingomyelinase activity in extracts of tissues or cells, in tears, and probably in hair follicles, as well as diagnose Niemann-Pick disease, either pre- or post-natally
Pattern of urinary proteins and peptides in patients with rheumatoid arthritis investigated with the Iso-Dalt technique.
Authors: Clark P M , Kricka L J , Whitehead T P 
Published: February 2020

Abstract
Characteristic differences in the pattern of urinary proteins and peptides have been found in patients with rheumatoid arthritis, compared with patterns from healthy controls. These differences have been demonstrated with a two-dimensional gel electrophoretic technique (Iso-Dalt) involving isoelectric focusing in the first dimension, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. Using simple photographic techniques, one can obtain a composite pattern of the individual protein-stained gels for each group. Comparison of the composite patterns from the rheumatoid arthritis group and the control group revealed several proteins in the urine of the rheumatoid arthritis patients not found in the control group. Two groupings of these proteins were identified: acidic, high-Mr proteins and more basic, low-Mr proteins.
Radioimmunoassay for detection of latent chronic alcoholic pancreatitis, an unrecognized clinical syndrome.
Authors: Nerenberg S T , Prasad R , Pedersen L D , Biskup N S 
Published: February 2020

Abstract
We developed a radioimmunoassay procedure in which we used an antibody monospecific for pancreatic acinar antigen, to sensitively and specifically test for the presence of subclinical (latent) alcoholic pancreatitis. The antigen was isolated, purified, and partially characterized. Results of testing appropriate populations of patients support the idea that chronic alcoholism is associated with chronic, subclinical damage to the pancreas and concomitant continuous release of a pancreatic acinar protein into the peripheral circulation, where it can be detected and quantitated. About 40% of the samples from chronic alcoholics (whether during a bout of acute alcoholism or during abstinence) demonstrated the circulating antigen, strongly suggesting that those alcoholics who will develop symptomatic, chronic alcoholic pancreatitis can be readily detected during the non-symptomatic stage.
Improved electrothermal determination of aluminum in serum by atomic absorption spectroscopy.
Authors: Alderman F R , Gitelman H J 
Published: February 2020

Abstract
We describe an improved method for determination of aluminum in serum by atomic absorption spectrophotometry with a graphite furnace. Interferences have been controlled and total combustion of the samples achieved by the use of new diluent in a molybdenum-treated graphite tube. The detection limit of this method is 2 microgram/L.
Gas-chromatographic determination of amantadine in human urine.
Authors: Stumph M J , Noall M W , Knight V 
Published: February 2020

Abstract
We describe a gas--liquid-chromatographic method for determining the concentration of amantadine hydrochloride in urine with beta-phenylethylamine as internal standard. The urine sample is made alkaline and extracted with 0.5 mL of chloroform. After centrifugation the aqueous layer is aspirated, and an aliquot of the organic layer is injected directly into the gas chromatograph. Concentration and instrument response are linearly related between 2 and 125 mg/L. The limit of detection was 0.5 mg/L. Mean analytical recovery was calculated to be 97%.
Incidence of a split alpha 2-glycoprotein band in the electrophoretic pattern for serum of adenocarcinoma patients.
Authors: Dermer G B , Silverman L M , Gendler S J , Tökés Z A 
Published: February 2020

Abstract
We electrophoresed serum samples on Mylar-backed cellulose acetate membranes and stained for glycoproteins with the periodic acid—Schiff reagent. The samples were from untreated adenocarcinoma patients, adenocarcinoma patients receiving chemotherapy, and patients with other malignancies, and also from patients with benign proliferative diseases, inflammatory diseases, and other non-malignant conditions. Forty-five per cent of the sera from untreated adenocarcinoma patients and 80% of those from adenocarcinoma patients with progressive systemic disease exhibited a splitting of the alpha 2-glycoproteins into a fast and slow band. Such a pattern was seen in only 4% of the non-adenocarcinoma cancer patients and 4% of the control group. Serial studies indicated that electrophoretic patterns of alpha 2-glycoproteins change with clinical status. Non-cancer patients with high concentrations of acute-phase proteins in their serum did not exhibit two alpha 2-glycoprotein bands. Further characterization of serum proteins from the fast alpha 2 region suggest that alpha 1-acid glycoprotein and haptoglobin beta chains are the principal components staining with periodic acid—Schiff reagent. These components are markedly less apparent in, or are absent from, the fast alpha 2 region of normal sera.
Hemoglobin determined in 15 microL of whole blood by "front-face" fluorometry.
Authors: Blumberg W E , Doleiden F H , Lamola A A 
Published: February 2020

Abstract
We describe the rapid, inexpensive fluorometry of hemoglobin in undiluted whole blood. The procedure consists only of adding a standard quantity of a fluorescent dye to a measured volume (approximately 15 microL) of blood, together with some solubilizing detergent. The assay is based on the attenuation of the dye's fluorescence (excited within the region 400—440 nm) that results from the competitive absorption of exciting light by the hemoglobin present—the "inner filter effect." The wavelength that one can use is optional and will determine which dyes can be used. Measurements are made with the hematofluorometer, a "front-face" filter fluorometer (Blumberg et al., J. Lab. Clin. Med. 89: 712—723, 1977). We demonstrate the validity of the method for two dyes, rhodamine B and fluorescein dibutyrate, which we used with hematofluorometers that were designed to determine blood zinc protoporphyrin and bilirubin, respectively. Our method exhibited a standard error of about 4 g of hemoglobin per liter vs the comparison method (Coulter Counter method, for which the CV is 1.2%). The CV is about 3%. The method seems appropriate for "field" use (i.e., use outside the laboratory) in anemia-screening programs.
An interlaboratory study of the determination of digoxin by immunoassay.
Authors: Fast D M , Hannon W H , Burtis C A , Bayse D D 
Published: February 2020

Abstract
We conducted a voluntary survey of laboratories and manufacturers to assess the current quality of analytical assays for serum digoxin. More than 300 clinical laboratories and 18 manufacturers responded, giving data on methods, instruments, computational procedures, and results for five survey samples. We sorted the analytical data to provide statistical information on the grand mean values separately for manufacturers and clinical laboratories, the frequency distribution of all reported values, and the mean values by method of interpolation and algorithms used for linear transformation. There was no statistical difference (alpha = 0.05) between the means for each specimen as determined by the kit manufacturers as a group and the clinical laboratories as a group.
Semiautomated homogeneous enzyme immunoassay of total serum thyroxine with a kinetic analyzer.
Authors: Bhatia H 
Published: February 2020

Abstract
A new semiautomatic procedure for determination of total serum thyroxine was adapted to a kinetic analyzer, LKB 2086 Mark II. The ABA thyroxine assay kit was used, and although the assay procedure was modified, the advantage of small reagent volumes, short measuring times, and automation were retained. The results were analyzed off-line with a programmable desk-top calculator. The method has a precision of 7% (CV) and a sensitivity of 8 nmol/L. Values in sera from 64 patients analyzed by enzyme immunoassay and by radioimmunoassay correlated well (r = 0.975). One kit contains enough reagents for 500 assays, and an operator could do 25 samples (i.e., 64 assays) in about 4 h.
Transient increase in serum creatine kinase isoenzyme BB activity after prostatectomy in a patient with massive benign prostatic hyperplasia.
Authors: Goodman Z D , Hamilton S R 
Published: February 2020

Abstract
The activity of creatine kinase isoenzyme BB (CK-BB) in serum is rarely abnormally high (i.e., detectable). An increase in immunoreactive CK-BB or CK-BB activity in patients with prostatic disease has been proposed as an indication of prostatic adenocarcinoma. Here we report the case of an elderly man with massive benign prostatic hyperplasia but no clinical or pathological evidence of prostatic adenocarcinoma, whose serum CK-BB activity was found by agarose gel electrophoresis to be 1 U/L (normal: 0%), 10% of his total CK activity. Serum CK-BB activity was further increased to 16 U/L (20% of total CK activity) 1 h after prostatectomy, but became undetectable by the second day after the operation. The findings suggest that: (a) the source of the serum CK-BB activity was the enlarged prostate gland; (b) abnormally high CK-BB activity in serum of men with prostatic disease does not necessarily indicate the presence of prostatic adenocarcinoma; and (c) myocardial injury could be erroneously diagnosed postoperatively in prostatectomy patients if CK isoenzyme methods are used that do not consistently separate "heart-specific" CK-MB from CK-BB.
A radioimmunoassay for 1,25-dihydroxycholecalciferol.
Authors: Bouillon R , De Moor P , Baggiolini E G , Uskokovic M R 
Published: February 2020

Abstract
We describe a radioimmunoassay for 1,25-dihydroxycholecalciferol in human serum. We raised antisera in rabbits to 1,25-dihydroxycholecalciferol-3-hemisuccinate coupled to bovine serum albumin, and obtained sensitive, high-titer antibodies. These antibodies had a high affinity for 1,25-dihydroxycholecalciferol and cross reacted mainly with 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol. Addition of 1 mL of normal rabbit serum per liter reduced this interference to 5 and 4%, respectively. However, these interfering steroids are present in large excess, so extensive purification of 1,25-dihydroxycholecalciferol from serum is necessary. The steroid was extracted with ethyl acetate/cyclohexane, purified on Sephadex LH-20, and then chromatographed on a column of silicic acid. The radioimmunoassay is sensitive to 5 pg/tube (3 ng/L of serum). The between-assay CV was 14%. The mean concentration of 1,25-dihydroxycholecalciferol in the serum of 54 healthy adults was 38 (SD 12) ng/L, with no sex-related difference. The assay was further validated by the finding of low or undetectable concentrations in patients with chronic renal failure and of increased concentrations in the serum of patients with primary hyperparathyroidism. In comparison with previously described methods, the major advantage of the present assay is the use of stable gamma-globulins, which are available in large amounts, as binding protein.
Automated creatine kinase-MB estimation by immuno-inhibition: a clinical evaluation.
Authors: Delahunty T J , Foreback C C 
Published: February 2020

Abstract
We detected the presence of creatine kinase (EC 2.7.3.2) MB isoenzyme (CK-MB) in serum by using an immunoinhibition technique to inactivate the creatine kinase isoenzyme of muscle origin (CK-MM). The GEMSAEC centrifugal analyzer is ideally suited for this procedure because it rapidly mixes reagents and has a throughput of 60 samples/h. The within-run CV was acceptable when the CK-MB value was 7.5 U/L or more. CK-MM was totally inactivated up to 5000 U/L, a value well above that usually seen in myocardial-infarct patients. We assessed the predictability of the assay for detecting myocardial infarction among 120 coronary-care patients when 2% of total CK activity was considered diagnostic and compared the results with those obtained with an electrophoresis technique. The positive predictive value of the immunoinhibition assay was 97.8%, as compared to 92% with the CK electrophoresis technique, when lactate dehydrogenase (EC 1.1.1.27) isoenzyme results were included in both cases. The optimal negative predictive value was 95.1% with the immunoinhibition assay vs 98.2% with electrophoresis. We conclude that the immunoinhibition technique for estimating CK-MB can be automated to assess myocardial status rapidly, precisely, inexpensively, and sensitively.
Serum high-density lipoprotein cholesterol concentrations in hypo- and hyperthyroidism.
Authors: Scottolini A G , Bhagavan N V , Oshiro T H , Abe S Y 
Published: February 2020

Abstract
We studied alterations in the concentration of high-density lipoprotein cholesterol and of other lipid categories (total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglycerides) in serum in hypo- and hyperthyroid states, and compared these findings with those of a control group. In the latter group the lipids showed an age-related increase in concentration but with a decrease in the eighth decade in all categories. In untreated hypo- and hyperthyroid subjects, all of the lipid values differed significantly from those of the controls but promptly returned to normal values upon treatment. In hypothyroid patients who are prone to develop coronary heart disease, the concentrations of high-density lipoprotein cholesterol were high, suggesting protection against heart disease, while the ratio to total cholesterol indicated the contrary. The exact opposite of these relationships was seen in hyperthyroid disorders. This apparent paradox suggests that the low-density lipoprotein cholesterol in serum, with its established atherogenic effect, should be given at least equal, if not more, weight than the concentration of high-density lipoprotein cholesterol in serum, with its alleged protective effect.
Purification of an alkaline phosphatase-lipoprotein-X complex.
Authors: Weijers R N , Kruijswijk H , Baak J M 
Published: February 2020

Abstract
An alkaline phosphatase isoenzyme was observed in an abnormal position in the agar-agarose gel pattern of sera from several patients suffering from intrahepatic and extrahepatic cholestasis. We purified this isoenzyme, by gel filtration and affinity chromatography, from the serum of a patient suffering from extrahepatic cholestasis. Analysis demonstrated an alkaline phosphatase-lipoprotein-X complex with a relative molecular mass of at least 669,000. We discuss the interpretation of alkaline phosphatase isoenzyme patterns produced by different techniques.