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Biomedical subjects

J K Lacki

Publications and source records attributed to J K Lacki.

At least 37 records · Page 2Linked to original sources
PubMed1995

Does the serum level of IgA-alpha-1-antitrypsin complex correlate with radiological progression in early rheumatoid arthritis? A 3-year follow-up study.

We followed the levels of serum IgA-alpha-1-antitrypsin (IgA-AT) complex in 37 patients with early rheumatoid arthritis (RA) during the first 3 years of the disease. The changes in IgA-AT were correlated with a radiological damage score (DS) of the hands assessed according to Larsen. At the onset of the disease, the IgA-AT serum concentration was significantly higher as compared to the control group (0.72 +/- 0.22 U vs 0.29 +/- 0.14 U, P < 0.01). The level significantly decreased during the 3-year observation period. The DS was significantly higher after 3 years. However, this difference was due to changes in only 11 patients; in 26 patients the DS was almost unchanged. In the group of 11 patients with radiological progression, the level of IgA-AT either remained high or increased significantly (0.95 +/- 0.18 U at the onset, 0.97 +/- 0.25 U after 3 years), whereas we observed a decrease in IgA-AT in 26 patients without radiological progression (0.63 +/- 0.16 U at the onset of the disease, 0.45 +/- 0.10 U after 3 years, P < 0.01). Moreover, a relationship between changes in IgA-AT serum level and radiological progression was shown (r = 0.60, P < 0.01). Our studies suggested that the relationship between IgA-AT level and radiological progression of the disease should be considered. We cannot exclude the possibility that the constant high level of IgA-AT may cause worsening in bone erosions.

Adolescent↗
PubMed1995

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: preliminary report.

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 +/- 18.1 pg/ml vs. 57.2 +/- 11.9 pg/ml). IL-6 level was significantly elevated (91.6 +/- 46.9 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 +/- 19 mg/l vs. 3 +/- 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

IgA-alpha-1-antitrypsin complex in systemic lupus erythematosus: preliminary report.

To investigate the role of the complex IgA-alpha-1-antitrypsin (IgA-AT) in systemic lupus erythematosus (SLE) and in mixed connective tissue disease (MCTD), and its possible relations to either activity of the disease or a treatment, we examined a concentration of IgA-AT complex in 65 SLE and 9 MCTD sera. Complex IgA-AT was evaluated using a double antibody enzyme-linked immunoassay (ELISA). Twenty nine patients with SLE (44.6%) and three patients with MCTD (33.3%) had increased serum IgA-AT levels. The mean values of IgA-AT complex in patients with SLE and MCTD were higher than in healthy controls. Among the SLE group, patients with current neurological manifestation were characterized by an increase in IgA-AT serum concentration (2.45 +/- 2.07 U vs. 0.78 +/- 0.70 U, P < 0.001). No relation was found between this complex and ESR level, C-reactive protein (CRP) concentration, or hemoglobin level. Ten SLE patients were treated with CTX intravenously. In this group of patients, IgA-AT complex level was found to be increased compared with patients without such a treatment (1.82 +/- 1.30 U vs. 0.80 +/- 0.67 U, P < 0.05). The present study provides two new observations. Firstly, IgA-AT complex is increased in SLE and MCTD compared with healthy controls, and secondly, patients with CNS involvement displayed a striking increased IgA-AT level.

Adult↗
PubMed1995

Do changes in clinical improvement in rheumatoid arthritis patients treated with immunosuppressive drugs reflect the changes in acute phase proteins?

We sought to investigate whether clinical improvement after immunosuppressive treatment reflects changes in acute phase response (APR) in rheumatoid arthritis (RA). Fifty-eight patients (pts) were treated with methotrexate (MTX), nineteen with intravenous cyclophosphamide (CTX), and fifteen with cyclosporin A (CSA). C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), alpha-1 antichymotrypsin (ACT), and alpha-1 antitrypsin (AT) serum levels were measured by nephelometry or rocket immunoelectrophoresis. Clinical improvement was observed in 67% MTX pts, 53% CTX pts, and 47% CSA pts. Baseline serum levels of CRP, AGP, ACT, and AT were significantly higher as compared to healthy controls. After MTX and CTX therapy CRP level significantly decreased. The decrease in serum level of ACT and AT in CTX treated patients was also observed. All analyzed acute phase proteins remained substantially elevated after CSA therapy despite a clear reduction in disease activity. We established a correlation between changes in disease activity and all acute phase proteins (APP) in MTX and CTX pts. From our study we can conclude that clinical improvement after immunosuppressive treatment correlated with quantitative changes in all APR markers in MTX and CTX treated pts, and none in CSA pts. Although measurement of APP remains the best marker for monitoring RA pts, not always they properly reflect changes in disease activity.

Acute-Phase Proteins↗
PubMed1995

The usefulness of CD4/CD8 ratio evaluation in monitoring of ovarian cancer patients.

Twenty-seven ovarian cancer patients were observed for twenty-four months. The patients were grouped as follows: Group I-with complete (CR) or partial remission (PR), Group II-with stable disease (SD), Group III-with progression (PD) of the disease. In all patients, T lymphocyte phenotypes were estimated in peritoneal fluid (PF) and in peripheral blood (PB). No differences were observed in either PF and PBT (CD3+) cell percentages among the examined groups of patients. A slight increase was noted in the percentage of CD4+ cells upon transition from the remission group to the groups with less favourable outcome of treatment. The increase was observed both in PB and in PF but only the latter showed statistically significant changes. On the contrary, percentage of T-cytotoxic/suppressor (CD8+) lymphocytes decreased upon transition from patients with the remission to those with stable disease and those with progression. These changes strongly affected the CD4/CD8 ratio. In PF, CD4/CD8 ratios were 2.13 +/- 0.9 and 4.18 +/- 1.6 in Group II and III, respectively (p < 0.01). In PB, the ratios were 1.88 +/- 1.1, 1.75 +/- 0.6, and 4.32 +/- 1.5 in Groups I, II and III respectively (Group I vs. Group III p < 0.01, Group II vs. Group III p < 0.01). During the study, five patients died due to ovarian cancer. In retrospective analysis, these patients showed progressive increase in CD4/CD8 ratio of PFT cells. Just before death, the ratio demonstrated an abrupt increase. In conclusion, the estimation of CD4+ and CD8+ cells as well as calculation of CD4/CD8 ratio for lymphocytes of peripheral blood and peritoneal fluid seems helpful in monitoring disease progression in ovarian cancer patients.

Adenocarcinoma↗
PubMed1995

Interleukin 10 inhibits interleukin 6 production and acute phase response in rheumatoid arthritis.

To evaluate the effect of interleukin 10 (IL-10) on acute phase response, we determined serum levels of IL-10, interleukin 6 (IL-6), C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), alpha-1-anti-chymotrypsin (ACT) in 34 rheumatoid arthritis (RA) patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). CRP, AGP and ACT levels were measured using rocket immunoelectrophoresis. The results showed that IL-10 serum level was increased in RA patients as compared to controls (60.0 +/- 17.5 pg/ml vs. 7.2 +/- 1.9 pg/ml). IL-6 level was significantly elevated (87.3 +/- 32.7 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (34 +/- 19 mg/1 vs. 3 +/- 2 mg/1, p < 0.05). AGP and ACT serum levels were increased in RA patients, but we did not find these changes to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.73, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.74, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. Moreover, a negative correlation between IL-10 and serum level of CRP (r = -0.76, p < 0.05), AGP (r = -0.60, p < 0.05) and ACT (r = -0.37, p < 0.05) was also shown. According to the data thus far obtained it seems that IL-10 decreases IL-6 production, and by that indirectly affects acute phase response, decreasing CRP, AGP and ACT synthesis.

Acute-Phase Reaction↗
PubMed1994

Comparison of microheterogeneity of alpha-1-acid-glycoprotein in serum and synovial fluid from rheumatoid arthritis patients.

Microheterogeneity of alpha-1-acid glycoprotein was studied using affinity immunoelectrophoresis with concanavalin A as a ligand in the samples of serum and synovial fluid obtained at the same time from 22 patients with rheumatoid arthritis. Individuals with intercurrent infection or other illnesses were excluded from the study. The results were expressed as reactivity coefficient (RC). Disease activity was evaluated by Mallya-Mace Activity Score, Lansbury Joint Index and laboratory tests. In most of the studied samples the glycosylation pattern was similar, composed of a nonreactive variant and 2 reactive (the first and the second) with Con A variants. In seven samples of synovial fluid an extra third peak representative of the strongly reactive one with Con A fraction was observed. It was the cause of the remarkable elevation of AGP-RC. Moreover, the level of IgM and IgA RF was higher in the synovial fluid derived from these patients--with the presence of the third peak in AFF-EP with Con A--than in those without the considered fraction.

Adult↗
PubMed1994

Lymphocyte phenotype studies of rheumatoid arthritis patients treated with methotrexate.

Seventy nine patients with rheumatoid arthritis (RA) were monitored for 12 months. Forty eight individuals were treated weekly with a low dose of methotrexate (MTX), and 31 received nonsteroid antiinflammatory drugs (NSAID) only. The mean total dose of MTX was 413 mg with a range from 250 to 735 mg. The phenotype of lymphocytes was analyzed using double immunofluorescence and a panel of monoclonal antibodies. The clinical status of 33 MTX-treated patients improved, in 9 neither clinical nor laboratory improvement was noticed. Six patients were withdrawn from the study because of adverse reactions. We observed no changes in the percentage of CD3, CD4, CD8 and CD25 positive lymphocytes in both MTX and NSAID-treated groups. However, the percentage of CD19 positive cells significantly decreased during 12 month observation (15.1 +/- 6.5% v.s. 10.2 +/- 5.0, p < 0.01) in MTX-treated subjects. Moreover, this percentage increased (9.4 +/- 6.7% v.s. 17.1 +/- 1.1%, p < 0.01) in NSAID-treated patients.

Adult↗
PubMed1994

Contrasting effect of oral and intravenous cyclophosphamide treatment on phenotypes of human peripheral blood lymphocytes.

Twenty three rheumatoid arthritis (RA) patients treated with cyclophosphamide (CTX) were observed for 6 months. Eight patients received CTX in a single intravenous dose (group I) and 15 orally in a single daily dose (group II). The surface antigens of lymphocytes, isolated from peripheral blood, were determined using immunofluorescence method. The clinical improvement was observed both in group I and in group II of patients. However, in patients receiving CTX intravenously amelioration of the disease appeared quicker. The percentage of CD3+ and CD8+ T cells remained unchanged. In group I we observed decrease in the number of CD4+ T cells (60.1 +/- 11.5% and 43.8 +/- 12.5%, before and after treatment respectively, p < 0.01), in group II this level remained unchanged. In both groups the percentage of CD19+ B cells decreased (14.7 +/- 9.2% and 8.0 +/- 6.1%, before and after treatment respectively in group I, p < 0.01; 17.4 +/- 12.3% and 11.0 +/- 7.1%, before and after treatment respectively in group II, p < 0.01). Moreover, the percentage of activated T cells (CD25+ cells and HLA-DR+ cells) was reduced in both groups.

Administration, Oral↗
PubMed1994

[Biological properties of interleukin 10].

Interleukin-10 (IL-10) is produced predominantly by T-helper lymphocytes and macrophages. IL-10 inhibits lymphocyte-induced cytokine production (CSIF--cytokine synthesis inhibitory factor), cooperates in B lymphocytes activation as well as macrophages--monocytes deactivation (MDF--macrophage deactivating factor). Due to its immunosuppressive properties IL-10 may be used in therapy of some T-cell induced diseases.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Quantitative changes in peripheral blood lymphocytes in erosive rheumatoid arthritis patients treated with methotrexate. Correlation with disease activity.

In order to better understand the immunological mechanisms involved in the pathogenesis of rheumatoid arthritis (RA), the level of various lymphocyte subsets in the peripheral blood of 29 patients with erosive RA was determined. All the patients were treated with methotrexate for 2 years. The total number and the proportion of CD3 cells, CD3+CD4+ and CD3+CD8+ cells did not change during the study. The initially increased level of CD19+ B-cells and CD19+CD5+ cells decreased during the treatment. The percentage of CD3-CD16+ natural killer cells was not affected by the treatment. At the inception of the study, we observed a deficiency of CD4+ CD45RA+ cells and the level of CD3+CD29+ cells was slightly increased. During the treatment we noticed significant elevation of CD45RA cells. Consequently, the CD29/CD45RA ratio significantly decreased. We showed significant correlation between changes in disease activity and changes in the level of CD19+ cells and CD4+CD29+ cells. Our results suggest that low-dose methotrexate may affect immunocompetent cells. The lowering in the CD29+ subset population associated with depletion of CD19 B-cells after methotrexate therapy may limit abnormal CD4+ cell activation and reduce the migration of lymphocytes into inflamed synovium.

Adult↗
PubMedDate not supplied

The presence of HLA-DR B1 shared motif does not influence cyclophosphamide and methotrexate cytotoxicity in rheumatoid arthritis patients.

In the present study we investigated the relation between cyclophosphamide and methotrexate toxicity and the presence of HLA- DR B1 alleles in rheumatoid arthritis patients. Seventy-eight such patients (67 women and 11 men) were observed for 12 months. Eighteen were treated with intravenous cyclophosphamide, 28 with oral methotrexate, and 32 with intramuscular gold salts. The prevalence of this shared motif was higher in the study population than in the healthy controls. However, detailed observations did not demonstrate a relation between particular genotype and drug intolerance. Based on the obtained findings we concluded that HLA-DR B1 typing cannot affect cyclophosphamide or methotrexate tolerance in rheumatoid arthritis patients. However, taking into account the relatively small number of patients expressing single genotype, further studies are recommended.

Adult↗
PubMedDate not supplied

Does the presence of HLA-DR B1 shared motif affect progression of the disease in rheumatoid arthritis patients?

The present study was undertaken in order to evaluate role of HLA DR Bl shared motif in prognosis of development of erosions in rheumatoid arthritis (RA). HLA genotyping was carried out in a retrospective analysis of 73 RA patients and 87 healthy controls using polymerase chain reaction. The assessment of disease activity was performed according to Mallya-Mace Index, whereas radiographs of hands were assessed according to the Larsen Index. HLA-DR4 and DR10 were significantly increased among RA patients. Relative risk was 7.540 and 4.646, respectively. Interestingly, the presence of DRl and DR14 did not enhance the relative risk in our group of patients. Determination of HLA-DR B1 alleles showed that among RA patients the most frequent was HLA-DR Bl&#x002A;0401, &#x002A;0404, and &#x002A;0408. They gave a rise to a relative risk of 4.010, 7.540, and 3.686 respectively. For the purpose of analysis the patients were divided into three groups. The first group comprised 14 patients with two high-risk alleles (HLA DR B1 &#x002A;01, &#x002A;0401, &#x002A;0404, &#x002A;0408, &#x002A;14). The second group gathered 35 patients with one high-risk allele. Twenty-four patients with no high-risk alleles were designated to the third group. We did not notice any differences in damage score and progression of damage score in rheumatoid arthritis patients with different number of high risk motifs. In conclusion, HLA-DR B1 shared motif was found to be significantly more frequent among analyzed erosive rheumatoid arthritis as compared to matched healthy controls. We did not observe any relation between the presence of shared motifs and outcome of the disease. Therefore, it seems that HLA DR B1 determination may very helpful in diagnosing or in establishing groups of risk but it is not likely to have a role in predicting development aggressive forms of RA.

Journal Article↗
PubMedDate not supplied

Does C-reactive protein modulate T-lymphocyte function in methotrexate-treated rheumatoid arthritis patients?

Thirty-four patients with rheumatoid arthritis were treated with oral methotrexate for 6 months. Methotrexate was given as a single weekly dose of 7.5-10 mg. A correlation between serum concentration of CRP and proportion of CD8+ lymphocytes in peripheral blood was found in this group of patients. This correlation can be described by a linear regression equation. According to the results obtained, CRP suppresses lymphocyte function in patients with RA. This is the consequence of the stimulating effect on suppressor mechanisms.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Acute-phase response in early refractory rheumatoid arthritis: long-term follow-up study.

In order to investigate the role of the acute-phase response in early rheumatoid arthritis (RA), we followed the changes of alpha 1-acid glycoprotein (AGP), alpha 1-antitrypsin (AT) and alpha 1-antichymotrypsin (ACT) in the sera of 25 patients with refractory rheumatoid arthritis (RA) during the first 3 years of the disease. Serum levels of AGP, ACT and AT were measured using rocket immunoelectrophoresis, and AGP, ACT and AT microheterogeneities were performed using two-dimensional immunoelectrophoresis with concanavalin A (Con A) as ligand. On average, serum levels of AGP, ACT and AT proteins were higher at the onset of the disease as compared with healthy controls. After 3 years, a significant decrease in serum levels of all three acute-phase proteins (APPs) was observed, but only in patients without anatomical progression was this decrease statistically significant. At the beginning of the study, only the AT reactivity coefficient (RC) was decreased in comparison with healthy subjects. However, after 3 years of disease, AGP, ACT and AT RCs all decreased. This investigation provided two new observations. The first is that only AT RC is significantly lower in comparison with normal values at the beginning of RA, whereas AGP RC and ACT RC remain within the normal range of values; a decrease in AGP RC and ACT RC appeared later. The second observation is that the highly elevated levels of APPs at the onset of RA decrease during the course of the disease. Moreover, this decrease does not depend on the disease activity, but a relationship with radiological progression was shown.

Acute-Phase Proteins↗