scholarly journals Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3404-3413 ◽  
Author(s):  
SP Stabler ◽  
J Lindenbaum ◽  
DG Savage ◽  
RH Allen
Keyword(s):  
Blood Donors ◽  
Pyridoxal Phosphate ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Folate Deficiency ◽  
Normal Range ◽  
Cystathionine Beta Synthase ◽  
Total Homocysteine ◽  
Chromatographic Mass

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.

scholarly journals Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3404-3413 ◽  
Author(s):  
SP Stabler ◽  
J Lindenbaum ◽  
DG Savage ◽  
RH Allen
Keyword(s):  
Blood Donors ◽  
Pyridoxal Phosphate ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Folate Deficiency ◽  
Normal Range ◽  
Cystathionine Beta Synthase ◽  
Total Homocysteine ◽  
Chromatographic Mass

Abstract Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.

scholarly journals Clinical and laboratory observations on serum folate-binding protein

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609 ◽  
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove
Keyword(s):  
Binding Protein ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Folate Level ◽  
Folate Binding Protein ◽  
Serum Folate Level ◽  
Relationship Of ◽  
The Relationship

Abstract We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.

scholarly journals Retrospective analysis of canine monocytic ehrlichiosis in Thailand with emphasis on hematological and ultrasonographic changes

2022 ◽  
pp. 1-9
Author(s):  
Kris Angkanaporn ◽  
Jidapha Sanguanwai ◽  
Taratip O. Baiyokvichit ◽  
Pichamon Vorrachotvarittorn ◽  
Montana Wongsompong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Elevated Serum ◽  
Serum Levels ◽  
Buffy Coat ◽  
The Body ◽  
Normal Range ◽  
Target Organs ◽  
Canine Monocytic Ehrlichiosis ◽  
Tick Borne Disease ◽  
Veterinary Hospital

Background and Aim: Canine monocytic ehrlichiosis (CME) is a tropical endemic tick-borne disease that causes fatality or chronic infection involving many organs in dogs. This study aimed to examine the prevalence, risk factors, and hematological and ultrasonographic changes in the liver, gallbladder, kidneys, and spleen following CME infection. Materials and Methods: This retrospective study used 30,269 samples collected from dogs at the hematology section of the pathology unit of a university veterinary hospital and 35 samples collected from dogs at the diagnostic imaging unit. CME was determined using the buffy coat smear method. Data were analyzed using descriptive statistics and odds ratios. Results: CCl4 The data revealed that the average yearly prevalence of CME was 1.32%. Risk factors contributing to CME infection were a tick on the body during physical examination, lack of ectoparasite control, and outdoor living. All 148 dogs with CME infection had low platelet counts. The percentages of CME-infected dogs with elevated serum alanine aminotransferase, alkaline phosphatase, and both enzymes above the normal range were 33.6%, 65.9%, and 29.8%, respectively. The rates for elevated serum levels of blood urea nitrogen, creatinine, and both compounds were 33.1%, 19.1%, and 17.3%, respectively. The most common ultrasonographic changes were liver abnormalities (hyperechogenicity or hypoechogenicity, hepatomegaly, and hypoechoic nodules), hyperechogenicity of the kidneys, and an enlarged spleen. These ultrasonographic changes were consistent with the hematology results, which showed a greater elevation of serum liver enzyme levels than renal enzymes. Conclusion: Ultrasonographic changes during CME infection and after treatment with doxycycline can help to monitor and identify persistent pathological changes in the target organs resulting from immune response to CME.

Evaluation of Cytokeratin 19 Serum Fragments (Cyfra 21–1) in Patients with Lung Cancer: Results of a Multicenter Trial

1994 ◽  
Vol 9 (2) ◽  
pp. 89-95 ◽  
Author(s):  
E. Bombardieri ◽  
E. Seregni ◽  
A. Bogni ◽  
S. Ardit ◽  
S. Belloli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Respiratory Diseases ◽  
Blood Donors ◽  
Stage Iv ◽  
Large Cell ◽  
Normal Subjects ◽  
Serum Levels ◽  
Multicenter Trial ◽  
Cytokeratin 19 ◽  
Significant Difference

Recently, a new immunometric assay (Cyfra 21–1) was developed to measure serum concentrations of a soluble fragment of cytokeratin subunit 19. With this method, supplied by Boehringer Mannheim (EIA Test Cyfra 21–1), an Italian multicenter trial was performed in patients with lung cancer. Cyfra 21–1 serum levels were determined in 568 normal subjects (blood donors), 607 patients with non-malignant diseases (491 respiratory diseases) and 730 patients with malignancies. In the latter group 584 had lung cancer. All these 584 patients had pathologically confirmed disease; 314 were epidermoid tumors, 166 adenocarcinomas, 88 small cell cancers and 16 large cell cancers. In the 568 healthy blood donors the mean Cyfra 21–1 value was 0.91 ng/ml (SD 0.47 ng/ml; range 0.05–2.90 ng/ml). A threshold of 1.9 ng/ml was chosen as the upper limit of normality. High levels of Cyfra21–1 were observed in patients with chronic hepatitis (positivity rate: 17/51–33.3%) and with pancreatitis (positivity rate 5/16 - 31.3%). In 114 out of 491 (23.2%) patients with respiratory diseases Cyfra 21–1 showed values greater than 1.9 ng/ml. The overall sensitivity (all stages) of Cyfra 21–1 in lung cancer was 65.6% (383/584). When the histology was considered the highest positivity rates were found in patients with squamous cell tumors (226/314; 72%) followed by adenocarcinomas (105/166; 63%). In patients with SCLC the global sensitivity was 52.3% (46/88). Higher sensitivity of Cyfra 21–1 was observed from stage I to stage IV (53.9% vs 85.7%; Chisquare: p < 0.01). When comparing patients in whom curative resections were possible (up to stage IIIa) with patients suffering from inoperable tumors, a significant difference in Cyfra 21–1 positivies was found (59% vs 81.5%; Chi square p < 0.01).

RELATION BETWEEN THYROID FUNCTION AND SERUM LEVELS OF LONG-ACTING THYROID STIMULATOR

1975 ◽  
Vol 79 (3) ◽  
pp. 451-458 ◽  
Author(s):  
J. C. Davis ◽  
L. J. Hipkin ◽  
V. K. Summers ◽  
T. M. D. Gimlette
Keyword(s):  
Thyroid Function ◽  
Normal Level ◽  
Normal Subjects ◽  
Serum Levels ◽  
The Other ◽  
Causative Role ◽  
Normal Range ◽  
The Mean ◽  
Long Acting ◽  
Normal Controls

ABSTRACT Bioassays of long-acting thyroid stimulator (LATS) were performed in three groups of subjects: in normal controls, in thyrotoxic patients before and serially after 131I treatment, and in patients with hypopituitarism. Of the untreated thyrotoxic patients, 27.7 % had raised serum LATS levels initially. There was no correlation between the relapse rate after 131I therapy and the initial or subsequent LATS titres: in particular, thyrotoxicosis sometimes recurred after an initially high LATS titre had fallen into the normal range. The distribution of the results of LATS assays in the hypopituitary patients was significantly different from that in the normal subjects; 4 out of 27 hypopituitary patients had LATS levels above the normal range, although they had no thyroxicosis. On the other hand, the majority of the patients with hypopituitarism, 19 out of 27, had LATS titres below the mean normal level, possibly due to deficiency of a substance we have termed pseudo LATS. These results raise doubts about a direct causative role for LATS in most cases of thyrotoxicosis.

scholarly journals Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets

2004 ◽  
Vol 183 (3) ◽  
pp. R1-R9 ◽  
Author(s):  
Doron Bresler ◽  
Jan Bruder ◽  
Klaus Mohnike ◽  
William D Fraser ◽  
Peter S N Rowe
Keyword(s):  
Elevated Serum ◽  
Fold Increase ◽  
Normal Subjects ◽  
Serum Levels ◽  
Hypophosphatemic Rickets ◽  
Normal Male ◽  
Renal Tubules ◽  
Mineral Density ◽  
Normal Individuals ◽  
Asarm Peptide

MEPE (Matrix Extracellular PhosphoglycoprotEin) expression is markedly elevated in X-linked-hypophosphatemic-rickets (HYP) and tumor-induced osteomalacia (TIO). In normal individuals, circulating serum-levels of MEPE are tightly correlated with serum-phosphorus, parathyroid hormone (PTH) and bone mineral density (BMD). Also, MEPE derived, C-terminal ASARM-peptides are candidate minhibins and/or phosphatonins. Our aims were to determine: 1. whether MEPE-ASARM-peptide(s) are abnormally elevated in HYP/hyp serum, and, 2. whether the ASARM-peptide(s) accumulate in hyp mice kidney renal-tubules. Using a specific competitive ELISA we measured a five fold increase (P=0.007) of serum ASARM-peptide(s) in human HYP patients (normal subjects 3.25 μM n=9; s.e.m.=0.51 and HYP-patients 15.74 μM, n=9; s.e.m.=3.32). A 6.23 fold increase (P=0.008) was measured in hyp male mice compared with their normal male siblings (normal-siblings, 3.73 μM, s.e.m.=0.57, n=3; and hyp-mice 23.4 μM, n=3, s.e.m.=4.01). Renal immuno-histological screening also revealed a dramatic increase of ASARM-peptides in regions anatomically consistent with the proximal convoluted tubules. This study demonstrates for the first time that markedly elevated serum levels of protease-resistant ASARM-peptide(s) occur in HYP/hyp and they accumulate in murine hyp kidneys. These peptides are thus likely responsible for the phosphaturia and defective mineralization in HYP/hyp and TIO.

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

scholarly journals Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 871-881 ◽  
Author(s):  
SP Stabler ◽  
RH Allen ◽  
DG Savage ◽  
J Lindenbaum
Keyword(s):  
Cell Volume ◽  
Peripheral Blood ◽  
Methylmalonic Acid ◽  
Peripheral Blood Smear ◽  
Normal Subjects ◽  
Lactic Dehydrogenase ◽  
Serum Levels ◽  
Cobalamin Deficiency ◽  
Mean Cell Volume ◽  
Total Homocysteine

Abstract To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

scholarly journals ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

1998 ◽  
Vol 40 (4) ◽  
pp. 219-224 ◽  
Author(s):  
Fernando Lopes GONÇALES Jr. ◽  
Raquel Silveira Bello STUCCHI ◽  
Priscila Maria Oliveira PAPAIORDANOU ◽  
Maria Helena Postal PAVAN ◽  
Neiva Sellan Lopes GONÇALES ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Blood Donors ◽  
Elevated Serum ◽  
Abdominal Ultrasound ◽  
Serum Levels ◽  
Gamma Glutamyl Transpeptidase ◽  
Period 2 ◽  
Increased Risk

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

scholarly journals Erythrocyte Vitamin B12 Activity in Health, Polycythemia, and in Deficiency of Vitamin B12 and Folate

Blood ◽  
1970 ◽  
Vol 35 (1) ◽  
pp. 73-82 ◽  
Author(s):  
A. OMER ◽  
N. D. C. FINLAYSON ◽  
D. J. C. SHEARMAN ◽  
R. R. SAMSON ◽  
R. H. GIRDWOOD
Keyword(s):  
Vitamin B12 ◽  
Pernicious Anemia ◽  
Plasma Levels ◽  
Normal Subjects ◽  
Folate Deficiency ◽  
Mean Value ◽  
Normal Range ◽  
The Mean ◽  
Secondary Polycythemia

Abstract A method for the estimation of vitamin B12 in erythrocytes using E. gracilis is described. In 29 normal subjects the mean value was 158 pg./ml. (S.D. 31 pg.) packed cells. Five of 14 patients with untreated primary polycythemia had very low erythrocyte vitamin B12 levels, and in the group as a whole the value was significantly less than normal. In eight patients with secondary polycythemia the erythrocyte vitamin B12 did not differ from normal, though two patients had values below the normal range. In 19 cases of pernicious anemia the mean erythrocyte vitamin B12 level was 53 pg./ml. (S.D. 32 pg.) packed cells which was significantly reduced. There was no constant relation between the erythrocyte and plasma levels. In eight cases of folate deficiency the erythrocyte vitamin B12 level was significantly reduced, with a mean value of 95 pg./ml. (S.D. 57 pg.) packed cells.

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