Activity In Sera Of Patients Research Articles

Increased Proapoptotic Serum Activity in Patients with Chronic Mood Disorders

Growing evidence suggests that endothelial dysfunction may be present in patients with chronic mood disorders. We hypothesized that circulating factors in the sera of patients with chronic mood disorders could induce vascular endothelial damage that in turn may be responsible for increased vascular risk. In this study, we sought to determine whether serum of patients with chronic mood disorders could directly induce apoptosis in human endothelial cells. We examined the proapoptotic activity by an ex vivo proapoptotic activity assay in the serum of 100 individuals: 25 patients with major depressive disorder (MDD) and no lifetime diagnosis of anxiety disorder, 25 patients with bipolar disorder (BPD) with a current comorbid anxiety disorder, 25 patients with BPD and no anxiety, and 25 age- and gender-matched healthy controls. The proapoptotic serum activity of all mood disorder patients was significantly higher than that of the control group (all p values<0.01). This association was found to be independent from potential confounders including age, gender, smoking status, body mass index, blood pressure parameters, family history of cardiovascular disease, serum creatinine, plasma glucose, total cholesterol, triglycerides, NT-proBNP, and C-reactive protein (beta=0.44, t=2.93, p=0.012). Together our findings indicate that chronic mood disorders are associated with higher proapoptotic serum capacity. Although subject to future confirmation, it is possible that the increased systemic proapoptotic activity of the serum in these patients could exert deleterious vascular effects resulting in endothelial dysfunction.

Adenosine deaminase activity in sera of patients with visceral leishmaniasis in India

Background Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Methods Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients at diagnosis and at posttreatment ( n = 22), healthy controls ( n = 15), patients with malaria ( n = 10), leprosy ( n = 10) and tuberculosis ( n = 10). Results Serum levels of ADA were significantly higher in active VL patients as compared to controls and patients with other diseases. ADA levels were also raised in patients with malaria, though not significantly as compared with active VL patients. Sera from VL patients at posttreatment showed significantly decreased ADA levels over sera from patients at diagnosis. Conclusions The results therefore suggest that ADA is involved in the pathogenesis and could be used as a clinical marker in the diagnosis of visceral leishmaniasis.

Biochemical Study of Antioxidants in Diabetic Patients

The research included a biochemical study of lipid peroxidation and other antioxidants and their relation with Diabetes Mellitus ( D.M.) type I (50 patients) and type II (100 patients). Measurement of some biochemical parameters were performed. The results of statistical analysis showed a significant increase of malondialdehyde peroxy nitrite radical and superoxide dismutase activity in serum of patients with type II when compared with normal. A significant decrease was also observed in concentration of vitamin C, vitamin E, glutathione, selenium, ceruloplasmine, uric acid and zinc in serum of diabetic patients of both types and peroxy nitrite radical in type I only. Other factors such as age, duration of the disease states, glucose concentration on lipid peroxidation and other antioxidants concentration were also performed. The results predicated that there was a significant increase in malondialdehyde with age in both types of diabetes and a significant decrease in serum concentration of vitamin C and E, glutathione with age in type II. A significant increase in MDA concentration with a decrease in vitamin C were also found in patients with increasing the duration of disease and a significant increase in malondialdehyde concentration with increasing blood glucose concentration, while there was a significant decrease in vitamin C and E concentrations.

Functional relevance of ceruloplasmin mutations in Parkinson's Disease

Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo-ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)-linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo-ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD.

Adenosine deaminase activity in sera of patients with visceral leishmaniasis in Nepal

This longitudinal study was conducted in BP Koirala Institute of Health Sciences (BPKIHS), a Medical University situated in eastern Nepal, between May 2001 and December 2001. The main objective of the study was to identify the role of adenosine deaminase (ADA) activity in patients with visceral leishmaniasis (VL) for management. There was a significant increase in mean ADA activity in sera of 49 patients with VL (323.71+/-184.51 IU/L) compared with 50 samples of control groups (47.11+/-24.94 IU/L) from the same endemic area (P < 0.001). ADA activities were found to be significantly decreased (50.35+/-41.35 IU/L) in follow-up cases (n = 19) after 30 days with sodium stibogluconate treatment at a dose of 20 mg/kg/day intramuscularly. The fall in the level of ADAF (after treatment) in follow-up cases correlated with the cure of disease, as evident from improvement of vital signs and symptoms and the absence of Leishmania donavani bodies in the sera. The study therefore suggests the possibility of using human serum ADA as a convenient marker to evaluate the diagnosis of VL to support the clinical findings, especially in those settings where there is a lack of highly qualified personnel and diagnostic facilities.

IL-6 and IL-10 Promoter Gene Polymorphisms of Patients and Donors of Allogeneic Sibling Hematopoietic Stem Cell Transplants Associate With the Risk of Acute Graft-Versus-Host Disease

The present study aimed to determine existing associations between single nucleotide polymorphisms within the promoters of interleukin (IL)-6 (-174 G/C) and IL-10 (-1082 G/A, -819 C/T, -592 C/A) genes and the outcome of allogeneic sibling hematopoietic stem cell transplantation. Ninety-three recipients and 74 donors were typed for IL-6 and IL-10 alleles by polymerase chain reaction-sequence specific primer. Then, IL-6 activity in patient serum and the concentration of C-reactive protein were analyzed at various times after transplantation in relation to transplant complications and IL-6 genotype. IL-6 activity in serum was significantly higher in patients who died as a result of toxic complications and after the 6 weeks after transplantation in patients with severe acute graft-versus-host disease (aGVHD). Recipient IL-6 G genotype was associated with increased IL-6 activity and C-reactive protein production. In univariate analyses, recipient IL-6 G and donor IL-6 GG associated or tended to associate with increased risk for aGVHD. In contrast, recipient IL-10 GCC/GCC and donor IL-10 ACC decreased the risk of aGVHD. IL-6 and IL-10 polymorphic features, together with other factors known to affect the risk of aGVHD, were also subjected to multivariate analyses. These analyses confirmed the independent contribution of recipient IL-10 GCC/GCC (odds ratio = 0.085, p = 0.046) and donor IL-6 GG (odds ratio = 3.934, p = 0.034) genotypes to the risk of aGVHD.

Antinucleosome Antibodies and Decreased Deoxyribonuclease Activity in Sera of Patients with Systemic Lupus Erythematosus

Nucleosomes are the dominant autoantigens in patients with systemic lupus erythematosus (SLE), and immune complexes involving nucleosomes are the major cause of tissue damage. The activity of DNase I, the enzyme responsible for nucleosome degradation, has been found to be decreased in patients with SLE. However, it is not known whether DNase activity is a clinically useful parameter. The aim of our study was to assess DNase activity in a prospective study of 113 patients with SLE in relation to disease activity and organ involvement. We included two control groups: 9 patients with undifferentiated connective tissue disease (UCTD) and 14 healthy individuals. DNase activity was found to be lower in patients with SLE (63.75%+/-12.1%) than in the controls (81.3%+/-9.25%) (P<0.001). DNase activity in patients with UCTD (64.9%+/-18.2%; P=0.854) did not differ from that in patients with SLE. Patients with SLE had higher antinucleosome antibody titers (356.3+/-851) than the controls (1.44+/-2.77; P<0.01) or UCTD patients (39.9+/-57.7; P<0.01). In addition, samples positive for antinucleosome antibodies displayed low levels of DNase activity. Within the SLE group, the presence of renal disease had no impact on DNase activity or antinucleosome antibody titers. Also, the SLE disease activity index showed no correlation with DNase activity. In a longitudinal study of six SLE patients, DNase activity did not follow disease activity or autoantibody titers. Our results confirm that serum DNase activity is decreased in patients with SLE, but we conclude that it is not a clinically useful parameter for the prediction of flare-ups of disease or renal involvement.

Nitric oxide level and superoxide dismutase activity in serum of patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disorder that is characterized by symmetric, erosive synovitis, sometimes with multisystem involvement. Inflammatory diseases such as RA are associated with increased production of nitric oxide (NO.), due to activation of the inducible nitric oxide synthase pathway. NO. is produced in increased amounts in inflammatory conditions and may cause tissue injury by reacting with superoxide to yield peroxynitrite, a powerful toxin. Superoxide dismutase (SOD) scavenges superoxide and inhibits the formation of peroxynitrite. We investigated SOD activity and NO. levels and their inter-relationships considering the disease activity. In this study, we measured erythrocyte sedimentation rate (ESR), serum SOD activity, NO. , and C-reactive protein (CRP) levels in 24 patients with rheumatoid arthritis. The control group consisted of 22 age- and sex-matched healthy subjects. In patients with RA, serum SOD activity and NO. levels were significantly higher than those of the control group. ESR and CRP levels were higher in patients with RA than in healthy subjects. Disease activity score (DAS) positively correlated with ESR, serum SOD activity, NO. , and CRP levels in patients with RA.

Sera from cancer patients contain two oscillating ECTO-NOX activities with different period lengths

ECTO-NOX protein’s are cell surface-associated and growth-related hydroquinone oxidases with both protein disulfide-thiol interchange activity and the capacity to oxidize NAD(P)H. The activities of these ECTO-NOX proteins are not steady state but fluctuate to create a repeating pattern of oscillations. Two forms of ECTO-NOX activities have been distinguished. The constitutive ECTO-NOX (CNOX), is hormone responsive and refractory to quinone-site inhibitors. A tumor-associated NOX (tNOX) is unregulated, refractory to hormones and growth factors and responds to quinone-site inhibitors. CNOX proteins are widely distributed and exhibit oscillations in enzymatic activity with a period length of 24 min. tNOX proteins are cancer specific and exhibit oscillations with a period length of about 22 min. Our findings now demonstrate the presence of the novel oscillating tNOX activity in sera of patients with cancer whereas the constitutive NOX of non-cancer cells is present in sera of both cancer patients and healthy volunteers. We conclude that ECTO-NOX proteins in sera exhibit oscillatory characteristics similar to those of ECTO-NOX forms of the cell surface.

Arginase in patients with breast cancer

The mean arginase activity in breast cancers ( n=80) was significantly higher than in control tissues and it accounted for 0.31±0.23 U/g wet tissue and 0.083±0.061 U/g ( P<0.05), respectively. With the cutoff value of 0.1 U/g wet tissue, raised arginase activity was observed in 74% of tumors. The preoperative arginase activity in blood serum from women with breast cancer was 11.2±7.9 U/l ( n=115), and it was significantly higher than in 70 healthy controls, where it was 5.7±2.4 U/l ( P<0.05). With the cutoff value for normal serum arginase activity above 8.0 U/l, the activity was raised in 10% of control individuals, and in 63% of women with breast cancer. The sensitivity and specificity of the arginase test in blood serum were 63% and 60%, respectively. Two isoforms immunologically identical to human kidney arginases ( l-arginine amidinohydrolase) were found in both normal and cancerous breast tissues. The level of anionic form was similar in control and cancerous tissues, whereas the cationic isoform predominated in breast cancer. The cationic isoform was the only one present in serum of both ill and healthy women, and its level was higher in patients with breast cancer. Thus, it can be concluded that the cationic isoform is responsible for the increase of arginase activity in serum of patients with breast cancer.

Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of autoantibodies and by systemic clinical manifestations and damage to multiple organs. The aim of the present study was to analyse matrix metalloproteinase (MMP)-9 activity in sera of patients with active and inactive SLE in order to evaluate its role in the pathogenesis and course of the disease, as well as its diagnostic value. We measured activity levels of MMP-9 and MMP-2, using both gel zymography and activity assay kits, in sera of 40 SLE patients and of 25 healthy controls. We found that MMP-9 activity, but not MMP-2 activity, is significantly elevated in the sera of SLE patients compared with sera samples of healthy controls. High activity levels of MMP-9 were determined in sera of 68% of the SLE patients. Elevated levels of MMP-9 were correlated with the presence of discoid rash, Raynaud phenomenon, pneumonitis, mucosal ulcers and anti-phospholipid antibodies. Changes in activity levels of MMP-9, but not of MMP-2, were observed in sera of the same patient at different periods of the disease course. High levels of MMP-9 did not correlate with disease activity index (SLEDAI, BILAG) in female patients, but correlated with SLE activity in the group of male patients. The results of the present study suggest that MMP-9 plays a role in the pathogenesis of SLE.

N-Acetylglucosaminyltransferase V as a possible aid for the evaluation of tumor invasiveness in patients with hepatocellular carcinoma.

A close relationship has been shown to exist between the metastatic potential and beta1-6 branched oligosaccharides in human and rodent cells. N-acetylglucosaminyltransferase V (GnT-V) catalyzes this process. Although this phenomenon has been reported, little is known about the clinical usefulness of the determination of GnT-V in the evaluations of tumor invasiveness in hepatocellular carcinoma (HCC). In this study, we measured the GnT-V activity in serum of patients with HCC, together with its activity and gene expression in HCC tissues, and elucidated the clinical usefulness of the GnT-V level in evaluating tumor invasiveness. Seventy-three serum samples from 38 patients with HCC, 11 with chronic hepatitis, eight with hepatic cirrhosis and 16 healthy controls were used. Twenty-one liver tissues were obtained by surgical resection from 17 patients with HCC, three with colorectal cancers and one with gallbladder cancer metastatic to the liver. The GnT-V activity was determined by using high performance liquid chromatography. The GnT-V mRNA was quantified by using competitive RT-PCR. There were statistically significant correlations between GnT-V activity in sera of HCC, and GnT-V activity and GnT-V mRNA expression in tumor tissue. The mean GnT-V activity in the sera of patients with HCC increased in accordance with the degree of tumor invasion. The HCC group with intrahepatic and extrahepatic metastases showed the highest serum GnT-V-value. The present study demonstrated that there was a close association between tumor invasiveness and GnT-V activity in sera, and that the measurement of GnT-V may improve prognostic estimates and therapeutic outcomes for patients with HCC.

Increased dipeptidyl peptidase IV activity in serum of patients infected with hepatitis C virus

Increased dipeptidyl peptidase IV activity in serum of patients infected with hepatitis C virus

Increased dipeptidyl peptidase IV activity in serum of patients infected with hepatitis C virus

Increased dipeptidyl peptidase IV activity in serum of patients infected with hepatitis C virus

β2-glycoprotein I-dependent Anticardiolipin Antibodies Preferentially Bind the Amino Terminal Domain of β2-glycoprotein I

Many of the autoantibodies in antiphospholipid syndrome (APS) are directed against beta2-glycoprotein I (beta2-GPI). Recent studies from our laboratories have indicated that the immunodominant binding epitope(s) for high titer, affinity purified antibodies from 11 APS patients are localized to the amino terminal domain (domain 1) of beta2-GPI. The present study employed surface plasmon resonance to localize the immunodominant domain in serum samples from a large cohort of patients with GPL values ranging from 21 to 230 units (n = 106 patients). Eighty-eight percent of patients showed > or = threefold selectivity for beta2-GPI containing domain 1 relative to the domain deletion mutant that lacked domain 1. The domain 1 binding activity in patient serum was abolished by removing the IgG fraction from the serum and the binding activity could be fully reconstituted with the IgG fraction. Thus, analysis of serum samples from a large cohort of APS patients indicates that the immunodominant binding epitope(s) for anti-beta2 antibodies are localized to the amino terminal domain of beta2-GPI.

Hyaluronidase activity in serum of patients with monoclonal gammapathy

Hyaluronidase and hyaluronic acid, two substances thought to be strongly implicated in carcinogenesis, were assessed in the plasma of 35 patients with newly documented monoclonal gammapathy and in 25 control patients. A significant increase was found in plasma hyaluronidase activity in the patients with monoclonal gammapathy. A statistically significant positive correlation was found between hyaluronidase activity and monoclonal immunoglobulin levels in plasma. An increase in serum hyaluronidase activities may be a response to the deleterious effect of hyaluronic acid in cell migration and tumor progression. Further studies are needed to assess the value of hyaluronidase activity as a marker of tumor progression.

Early pregnancy factor activity in serum of patients with surgical abortion.

The presence of early pregnancy factor (EPF) has been repeatedly confirmed as indispensable to successful pregnancy. However, there is as yet little reported about how surgical abortion would affect the EPF activity, owing to the induced embryo loss. The aim of this study was to pursue this among a large number of patients available in the People's Republic of China. Sera from aborters were collected before surgical abortion and again on the 3rd, 5th and 7th day after treatment. EPF activity was detected by rosette inhibition assay. Before surgical abortion, the mean level of EPF in pregnancy sera was about the same as that of the positive control. After surgical abortion, the EPF level declined rapidly for the first 3 days and then dropped gradually within the negative control range after 5-7 days. Quantitative study of EPF activity along temporal dimensions (duration) due to surgical abortion further promotes the efficiency to take EPF activity and its rate of change as truly index for monitoring embryonic care and development of normal pregnancy.

Adenosine deaminase and guanosine deaminase activities in sera of patients with viral hepatitis.

In order to investigate purin and primidin metabolism pathways in hepatitis, adenosine deaminase (ADA) and guanosine deaminase (GDA) activities in sera of patients with different types and manifestations of viral hepatitis disease (A, B, C, D, E, chronic, acute) were investigated and compared with the control group of healthy individuals. Hepatitis cases were classified with respect to their serological findings and clinics. When compared all the hepatitis cases with the controls, levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase enzymes, as well as ADA and GDA, were significantly higher than the control group (p<0.01). Levels of ADA and GDA in hepatitis cases were determined as 26.07 11.98 IU/l and 2.37 1.91 IU/l, respectively. When compared their ADA and GDA levels amongst the classified hepatitis groups, there was no difference in ADA levels amongst cases (p>0.05). However, GDA levels in hepatitis A group were closed to the controls. Increase in serum ADA activities in hepatitis forms may be dependent on and reflect the increase in phagocytic activity of macrophages and maturation of T-lymphocytes, and may be valuable in monitoring in viral hepatitis cases.

Superoxide dismutase activity in serum of patients with acute cerebral ischemic injury. Correlation with clinical course and infarct size.

Superoxide dismutase (SOD) is one of the major free radical scavenging systems that might play a role in both degenerative and acute diseases of the central nervous system. We measured SOD activity in the serum of 41 patients with acute ischemic stroke with a chemiluminometric assay based on the generation of oxygen free radicals by xanthine and xanthine oxidase. SOD activity was significantly lower in patients with ischemic stroke than in age-matched control patients with nonvascular, neurological illnesses (n = 24; P < .034, Wilcoxon rank test). The activity was inversely correlated with the size of infarction on CT (P = .01, Spearman correlation) and the severity of neurological deficits (P < .001, Spearman correlation). The decreased SOD activity recovered within 5 days after stroke to values found in serum of control patients. Our data suggest that the SOD activity in serum is reduced in stroke patients, and replacement of antioxidative activity could be beneficial in the acute treatment of cerebral ischemia.

Antibody and antibody-dependent cellular cytotoxicity responses against the BamHI A rightward open-reading frame-1 protein of Epstein-Barr virus (EBV) in EBV-associated disorders.

Antibody-dependent cellular cytotoxicity (ADCC) is an important antiviral effector mechanism. ADCC to the protein encoded by the Epstein-Barr virus (EBV) BamHI A rightward open-reading frame-1 (BARF1) was studied by transducing Raji-tk- cells with the BARF1 gene using a retroviral expression vector. The transduced Raji cells expressed BARF1 on the cell surface, as determined by flow cytometry. Sera from chronic and acute infectious mononucleosis and nasopharyngeal carcinoma patients were found to contain antibodies that react with the BARF1 protein. When BARF1-expressing Raji cells were used as targets for ADCC, sera from several nasopharyngeal carcinoma patients demonstrated significant ADCC reactivity, whereas sera from healthy EBV-seronegative and -seropositive persons lacked such reactivity. BARF1-specific ADCC activity could be competitively inhibited with recombinant BARF1 protein. The level of anti-BARF1 antibody activity in sera of patients with EBV-associated diseases suggests that the BARF1 protein may serve as a target on EBV-infected cells for ADCC.